Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human crescentic glomerulonephritis

AIMS: In glomerulonephritis, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) may play important roles in the formation of crescents. These studies are designed to evaluate the expression patterns of ICAM-1 and VCAM-1 in human crescentic glomerulonephritis and to determine the cellular origin of adhesion molecules in the crescentic lesions. METHODS AND RESULTS: We examined the expression of ICAM-1 and VCAM-1 proteins in renal biopsies with cellular (n=7), fibrocellular (n=9) or fibrous (n=4) crescentic glomerulonephritis, and six controls by immunohistochemistry. mRNA expression of ICAM-1 and VCAM-1 was further evaluated by RNA in-situ hybridization. Cytokeratin or CD68 immunohistochemistry was performed on the same sections, where in-situ hybridization had been carried out. In cellular crescents, ICAM-1 and VCAM-1 proteins were over-expressed to a similar extent. Of the three types of crescents, the extent of ICAM-1 immunopositivity was the greatest in the cellular crescents and decreased towards the fibrous crescents (P < 0.05). Yet the extent of VCAM-1 immunoreactivity was not different between the types. Fibrous crescents still contained some epithelial cells and showed only VCAM-1 expression. In the glomeruli with cellular or fibrocellular crescents, the extent of ICAM-1 immunopositivity in the glomerular tufts was significantly larger than that of VCAM-1 (P < 0.05). In an in-situ hybridization study, the mRNA expression patterns of ICAM-1 and VCAM-1 paralleled their protein expressions. A double-labelling study showed that the signal for ICAM-1 and VCAM-1 mRNAs was mainly present in cytokeratin-positive and CD68-negative cells in the crescentic lesions. CONCLUSIONS: These results suggest that glomerular parietal epithelial cells in cellular crescents up-regulate both ICAM-1 and VCAM-1, and that some epithelial cells retained in fibrous crescents persistently over-express VCAM-1, but not ICAM-1. They also suggest that ICAM-1 is involved in early leucocyte recruitment into glomeruli in crescentic glomerulonephritis.     

Adhesion molecule expression in vivo on extraocular muscles (EOM) in thyroid-associated ophthalmopathy (TAO)

TAO is an autoimmune condition characterized by mononuclear cell infiltration of the extraocular muscles (EOM) and/or the orbital fat/connective tissue with associated deposition of glycosaminoglycans (GAG) in the interstitial spaces. In this study, the presence and distribution of the vascular adhesion molecules intercellular adhesion molecule-1 (ICAM-1), endothelial-leucocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and the leucocyte integrins CD11a/CD18, CD11b/CD18, CD11c/CD18 were investigated. Nineteen EOM biopsies were collected from 17 patients with early (n = 6) and late (n = 13) TAO as well as from 12 non-TAO control patients. Consecutive cryostat sections of these biopsies were immunostained with MoAbs to the above-mentioned molecules and haematoxylin and eosin. Primary antibody binding was visualized using an avidin-biotin system. In early untreated TAO specimens, the interstitial and perimysial connective tissue surrounding EOM fibres and numerous mononuclear cells stained strongly for ICAM-1. In contrast, the vascular endothelial cells (ulex lectin-positive) stained strongly for ELAM-1 (E-selectin), VCAM-1 as well as ICAM-1. In late disease, the same distribution of immunoreactivity for ICAM-1, ELAM-1 and VCAM-1 was observed, but with significantly lower staining. The leucocyte integrins (CD11a, CD11b, CD11c) were again expressed at significantly higher levels in early TAO specimens compared with late TAO specimens and were minimal or absent in the EOM biopsies harvested from control patients. In conclusion, increased expression of adhesion molecules studied correlated with early active disease and was reduced in later stages.     

The distribution of adhesion molecules in human atherosclerosis

Chronic inflammatory cells are a recognized component of atherosclerotic plaques at all stages of development. As adhesion molecules play a fundamental role in inflammatory processes, we have carried out an immunohistochemical investigation of the distribution of endothelial leucocyte adhesion molecule-1 (ELAM-1)*, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human atherosclerotic lesions. Autopsy specimens from abdominal aorta and coronary arteries were obtained from 21 cases within 24 h of death. ELAM-1 and ICAM-1 were consistently expressed by the entire intimal endothelium of normal coronary arteries and also by the intimal endothelium overlying aortic fatty streaks. Both coronary artery and aortic lesions showed strong staining for ICAM-1 on and around macrophages. VCAM-1 was not detected on intimal endothelial cells, but strong staining of adventitial lymphoid aggregates for this molecule was seen. This work suggests a role for ELAM-1 and ICAM-1 in mononuclear cell recruitment during atherogenesis.     

Direct interaction with primed CD4+ CD45R0+ memory T lymphocytes induces expression of endothelial leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1 on the surface of vascular endothelial cells.

The process of recruitment of leukocytes at sites of inflammation involves direct cell-to-cell interactions between leukocytes and vascular endothelial cells (EC) mediated by various adhesion receptors on leukocytes and their inducible endothelial ligands. In this study we have examined the induction on EC of endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) upon their interaction with subpopulations of human T cells. When co-cultured with EC both resting CD4+ T and CD8+ T cells caused a modest increase in the expression of endothelial ICAM-1. Moreover, resting CD4+ but not CD8+ T cells induced expression of ELAM-1 and VCAM-1 on a small fraction of unstimulated EC. Prior activation with phorbol 12-myristate 13-acetate (PMA) significantly increased the ability of T cells to up-regulate endothelial ICAM-1 and also induced the expression of both ELAM-1 and VCAM-1. PMA-primed CD4+ T cells induced both VCAM-1 and ELAM-1 on EC more efficiently than CD8+ T cells. Furthermore, the ability to induce the expression of ELAM-1 and VCAM-1 was confined to the CD4+ CD45R0+ memory/primed subpopulation of T cells. This induction of various endothelial adhesion ligands could also be mediated by antigen-primed CD4+ T cell lines. The CD4+ T cell-mediated induction of adhesion ligands required direct intercellular contact with EC because neither cultures of EC and PMA-primed CD4+ T cells separated by a microporous membrane insert nor the conditioned medium of PMA-primed T cells induced expression of ELAM-1 and VCAM-1 on EC. Cyclosporin A significantly inhibited the activation of T cells with PMA but had no effect on the ability of PMA-primed T cells to up-regulate endothelial CAM. Thus, CD4+CD45R0+ T cells via as yet unknown mechanism can significantly enhance the expression of each of the three endothelial adhesion ligands and, thereby, may facilitate the process of recruitment of additional leukocytes to exacerbate inflammation.     

Endothelial and epithelial cell adhesion molecules

This review will discuss a number of specific cell adhesion molecules present on the surface of endothelial and epithelial cells in the lung. Molecules such as integrins, proteoglycans, and the hyaluronic acid receptor, CD44, are found on the abluminal or basement membrane side of the cell and function as cell-substratum receptors. Cadherins, integrins, and platelet-endothelial cell adhesion molecule-1 (PECAM-1) are present at the cell-cell borders of adjacent endothelial and/or epithelial cells and function to initiate or maintain cell-cell adhesion. Finally, a number of inducible cell adhesion molecules such as endothelial-leukocyte adhesion molecule-1 (ELAM-1), granule-associated membrane protein 140 (GMP140), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are expressed on the luminal surfaces of these cells during inflammation and function as cell-cell adhesion molecules important in white blood cell, platelet, or tumor cell adhesion. These adhesion molecules likely play important roles in maintaining the normal structure and function of the lung, as well as participating in pulmonary processes such as inflammation, wound healing, and the development and spread of malignant disease.     

Stimulation with thromboxane A2 (TXA2) receptor agonist enhances ICAM-1, VCAM-1 or ELAM-1 expression by human vascular endothelial cells

A previous study reported that intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells (HUVEC) is augmented by intracellular signal transmission mainly through the protein kinase C (PKC) system stimulated by TXA₂ receptors. In the present study, we show that a TXA₂ receptor agonist, U46619, augments the expression of not only ICAM-1, but also vascular cell adhesion molecule-1 (VCAM-1) or endothelial leucocyte adhesion molecule-1 (ELAM-1) in HUVEC both at protein and mRNA levels. Pretreatment with SQ29,548 (a TXA₂ receptor antagonist) or PKC inhibitors greatly diminished the extent of U46619-induced mRNA accumulation and surface expression of the adhesion molecules. An inhibitor of nuclear factor κB (NF-κB) activation, PDTC, diminishes U46619-induced VCAM-1 mRNA accumulation. NAC, which inhibits NF-κB and activation protein 1 (AP-1) binding activity, inhibits the expression of ICAM-1 or ELAM-1 at protein and mRNA levels. These findings suggest that ICAM-1 or ELAM-1 expression of HUVEC stimulated via TXA₂ receptors is augmented by induction of NF-κB and AP-1 binding activity through the PKC system, and that VCAM-1 expression is augmented by induction of NF-κB binding activity.     

Expression and cell distribution of the intercellular adhesion molecule, vascular cell adhesion molecule, endothelial leukocyte adhesion molecule, and endothelial cell adhesion molecule (CD31) in reactive human lymph nodes and in Hodgkin''s disease.

The immunocytochemical expression of intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), endothelial leukocyte adhesion molecule (ELAM-1), endothelial cell adhesion molecule (EndoCAM CD31), and HLA-DR antigens was investigated in sections of 24 reactive lymph nodes and in 15 cases of Hodgkin's disease. ICAM-1 was detected in sinus macrophages, follicular dendritic reticulum cells (FDRCs), interdigitating reticulum cells (IDRCs), epithelioid macrophages, Hodgkin's cells (HCs), and vascular endothelium. ICAM-1 expression was often associated with that of HLA-DR antigens. VCAM-1 was detected in FDRCs, in fibroblast reticulum cells (FRCs), in macrophages, and in rare blood vessels. EndoCAM (CD31) was constitutively expressed in all types of endothelial cells, sinus macrophages, and in epithelioid granulomas. ELAM-1 was selectively expressed by activated endothelial cells of high endothelium venules (HEVs). When expression of the inducible adhesion molecules ICAM-1, VCAM-1 and ELAM-1 was comparatively evaluated in HEVs, it was found that ICAM-1 + HEVs were present in all reactive and HD nodes, whereas ELAM-1 and/or VCAM-1 were expressed only in those pathologic conditions characterized by high levels of interleukin-1/tumor necrosis factor (IL-1/TNF) production, such as granulomatosis and Hodgkin's disease. In Hodgkin's disease, the expression of ELAM-1/VCAM-1 was more pronounced in cases of nodular sclerosis and was associated with a significantly higher content of perivascular neutrophils.     

Elevated expression in situ of selectin and immunoglobulin superfamily type adhesion molecules in retroocular connective tissues from patients with Graves' ophthalmopathy.

Activation of certain adhesion molecules within vascular endothelium and the surrounding extravascular space is a critical event in the recruitment and targeting of an inflammatory response or autoimmune attack to a particular tissue site. We have recently demonstrated that the adhesion of lymphocytes to cultured retroocular fibroblasts obtained from patients with Graves' ophthalmopathy (GO) is mediated predominantly by the interaction of lymphocyte function-associated antigen-1 (LFA-1), expressed on lymphocytes, with intercellular adhesion molecule-1 (ICAM-1), expressed by these cells following exposure to interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), IL-1 alpha or purified thyroid-stimulating immunoglobulins. We now report the expression and localization in situ of several adhesion molecules, ICAM-1, endothelial leucocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and LFA-3 in retroocular tissues derived from patients with severe GO (n = 4) and normal individuals (n = 3). Serial cryostat sections of tissue specimens were processed for immunoperoxidase staining using various MoAbs against ICAM-1, ELAM-1, VCAM-1 and LFA-3. In addition, consecutive sections were stained with MoAbs against LFA-1, CD45RO (UCHL-1)DR-human leucocyte antigen (HLA-DR), CD11b/CD18 (Mac-1), and CD11c/CD18 (p150,95). In GO-retroocular tissues, strong immunoreactivity for ICAM-1 and LFA-3 was detected in blood vessels (> 90%), in perimysial fibroblasts surrounding extraocular muscle fibres, and in connective tissue distinct from extraocular muscle. No ICAM-1 or LFA-3 immunoreactivity was present in extraocular muscle cells themselves. ICAM-1 and LFA-3 immunoreactivity in normal tissues was minimal or absent both in connective and muscle tissues. Vascular endothelium was strongly positive for ELAM-1 and VCAM-1 in GO-retroocular tissues, while VCAM-1 immunoreactivity was minimal (< 5% of blood vessels) and ELAM-1 immunoreactivity was generally absent in normal retroocular tissue. LFA-1-expressing, activated mononuclear cells and memory T lymphocytes (CD3+/CD45RO+) were only detected in GO-retrocular tissues, and were mainly localized around blood vessels and in areas of ICAM-1-expressing connective and perimysial tissue. HLA-DR expression was restricted to GO-tissue specimens, with strong immunoreactivity detected in blood vessels, macrophages and connective tissue and perimysial fibroblasts. No HLA-DR was detectable in extraocular muscle cells. In conclusion, infiltration of the orbit in GO by mononuclear cells, and their targeting within the orbit, may depend upon the coordinate expression of certain adhesion and MHC molecules.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of human cytomegalovirus and glucose on adhesion molecules expression in cultured human endothelial cells

The aim this study was to investigate the effect of glucose on the induction of adhesion molecules by Human cytomegalovirus (HCMV) in endothelial cells in vitro. Primary cultures of human umbilical vein endothelial cells (HUVECs) pretreated with 16.5 mmol/l glucose for 24 hrs were infected with a HCMV strain with tropism for endothelial cells. Expression of adhesion nmolecules (ICAM-1, VCAM-1 and ELAM-1) was measured by flow cytometry. While high concentrations of glucoseperse activated the expression of all three adhesion molecules tested, HCMV induced the expression of ICAM-1 only. Moreover, it potentiated the expression of ICAM-1 in glucose-pretreated HUVECs, while it did not affect at all or slightly suppressed the glucose-activated expression of VCAM-1 and ELAM-1. The modulatory effect of glucose and HCMV on the expression of adhesion molecules in endothelial cells may be applied in increased vulnerability to patients with diabetes mellitus or atherosclerosis.     

Adhesion molecules in atopic dermatitis: VCAM-1 and ICAM-1 expression is increased in healthy-appearing skin

In the skin of normal and atopic individuals, the expression of E-selectin (ELAM-1), L-selectin (LECAM-1), P-selectin (CD62), CD31 (PECAM), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and cutaneous lymphocyte antigen (CLA) were compared by immunostaining of skin biopsies which were taken from normal individuals ( n = 17), the healthy-appearing skin of patients with atopic dermatitis ( n = 10), and their acute ( n = 5) and chronic ( n = 6) skin lesions. In contrast to ELAM-1, the expression of VCAM-1 and ICAM-1 was found to be significantly increased in nonlesional atopic skin in comparison to the skin of normal individuals. Moreover, in contrast to normal skin of healthy individuals, nonlesional atopic skin showed a further increase of VCAM-1, ICAM-1, and ELAM-1 when cultured with medium alone. This suggests that certain adhesion molecules are constitutively upregulated in healthy-appearing skin of patients with atopic dermatitis. In addition, atopic skin appears to respond to nonspecific stimuli (such as culture with medium alone) with upregulation of VCAM-1, ICAM-1, and ELAM-1. It is suggested that the observed upregulation of adhesion molecules is mediated by the release of cytokines such as interleukin-4 from cells which reside in atopic skin. The question of whether the inherent upregulation of adhesion molecules in atopic skin contributes to the development of Th2 cells, which have been found to predominate in atopic inflammation, has to be further investigated.     

Adhesion molecule expression in Graves'' thyroid glands; potential relevance of granule membrane protein (GMP-140) and intercellular adhesion molecule-1 (ICAM-1) in the homing and antigen presentation processes.

To assess the potential role of adhesion molecules in the pathogenesis of Graves' disease, we examined the expression of several of these adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM-1) and granule membrane protein-140 (GMP-140), in sections of Graves' thyroid glands and control thyroids, using immunohistochemical techniques. Up-regulated expression of GMP-140 was frequently observed on endothelial cells (EC) of post-capilliary venules in all Graves' thyroids examined, compared with an occasional weak staining on EC control glands. Some capillary EC around thyroid follicles (perifollicular EC) were strongly positive for GMP-140 in the Graves' thyroids in contrast to a negative staining on the same structures in the control glands. In addition, there was a correlation between the reactivity and frequency of GMP-140 expression on EC and the severity of mononuclear cell (MNC) infiltration in the Graves' thyroids. The expression of ICAM-1 was up-regulated on perifollicular EC and EC of small venules in some thyroids of both Graves' and control groups. Conversely, no significant expression was observed on any type of EC for both endothelial-leucocyte adhesion molecule-1 (ELAM-1) and VCAM-1. However, dendritic-like cells, present within lymphocytic infiltrates, were positive for VCAM-1 in most of the Graves' thyroids examined, especially in those with a severe lymphocytic infiltration. Thyrocytes were constantly negative for the expression of all four adhesion molecules investigated. These data suggest that GMP-140, as well as ICAM-1, could play an important role in the initiation of MNC infiltration in Graves' disease. ELAM-1 and VCAM-1 appear not to be relevant for the migration of MNC from the blood vessels into the target gland, although VCAM-1 expression on dendritic-like cells might play an additively tissue-selective role in autoantigen presentation and subsequent elicitation of autoimmune phenomena.     

Morphological analysis of leucocyte transmigration in the pleural cavity

The role that pleural mesothelial cells play in leucocyte transmigration into the pleural cavity was investigated in lipopolysaccharide-stimulated mice. Changes in mesothelial cell morphology and changes in expression of adhesion molecules on mesothelial cells and leucocytes were analysed by light microscopy, immunohistochemistry, transmission electron microscopy (TEM) and immuno-scanning electron microscopy (immuno-SEM). After stimulation, the mesothelial cells separated completely from one another before leucocyte penetration across the mesothelial layer occurred. These changes occurred primarily in the immediate vicinity of ribs, where a large number of leucocytes accumulated. Immuno-SEM showed that the expression of intercellular adhesion molecule-1 (ICAM-1) on the parietal pleural mesothelial cells was significantly up-regulated by lipopolysaccharide stimulation, and that of vascular cell adhesion molecule-1 (VCAM-1) was induced. Both were restricted to the microvilli of the mesothelial cells. By contrast, expression of intercellular adhesion molecule-2 (ICAM-2), platelet/endothelial cell adhesion molecule-1 (PECAM-1), mucosal addressin cell adhesion molecule-1 (MAdCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), peripheral node addressin (PNAd) and fibronectin were not detected. Lymphocyte function associated antigen-1 (LFA-1), macrophage-1 molecule (Mac-1) and very late appearing antigen-4 (VLA-4), all ligands of ICAM-1 and VCAM-1, were present on the transmigrated neutrophils and macrophages. These findings demonstrate that the immediate vicinity of ribs is a source of leucocyte migration into the pleural space.     

Ultrastructural localization of vascular cell adhesion molecule-1 in proliferative and crescentic glomerulonephritis

Recent studies have demonstrated an important role of vascular cell adhesion molecule-1 (VCAM-1) in the pathogenesis of nephritis. In the present study, renal biopsy specimens from patients with proliferative and crescentic glomerulonephritis were subjected to immunoelectron microscopy using an anti-VCAM-1 monoclonal antibody. In control normal kidney tissue, VCAM-1 expression was restricted to the free surface of parietal epithelial cells. In diseased glomeruli, VCAM-1 was expressed on the free surface of parietal and visceral epithelial cells, on the luminal surface of capillary endothelial cells, on infiltrating monocyte/macrophage-like cells, on mesangial cells, and in the matrix of the expanded mesangium. There was also VCAM-1 expression on almost all cell types in the crescents, including macrophage-like cells, fibroblast-like cells, and epithelial cells. Some cells also showed VCAM-1 positivity in the rough endoplasmic reticulum and the perinuclear space. Both the glomerular capillary lumen and urinary spaces of Bowman's capsule contained positive reaction products, which were often associated with exocytosis by the surrounding cells. VCAM-1 was predominantly expressed on the basal and lateral surfaces of a few proximal tubules, but it could not be localized ultrastructurally. These findings suggest that production and secretion of VCAM-1 by both infiltrating monocyte/macrophages and resident glomerular cells may be related to the pathogenesis of proliferative and crescentic glomerulonephritis.     

The expression of leukocyte-endothelial adhesion molecules is increased in perennial allergic rhinitis.

Accumulating evidence supports the importance of leukocyte-endothelial cell adhesion molecule (CAM) expression as an initiating process in tissue inflammation. To investigate the relevance of CAM expression to allergic airways inflammation, nasal biopsies from patients with perennial allergic rhinitis (n = 8) and from nonatopic healthy volunteers (n = 8) were immunostained with monoclonal antibodies directed against the CAMs, intercellular adhesion molecule-1 (ICAM-1), endothelial cell adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). The endothelial staining of these CAMs was related to the number of vessels within each biopsy, delineated by a monoclonal antibody against Ulex europaeus-1 lectin bound to endothelial cells, and to the number of tissue leukocytes staining for one of the ligands of ICAM-1, the beta 2 integrin, lymphocyte function-associated antigen (LFA-1). Expression of CAMs was related to the number of infiltrating neutrophils, eosinophils, and lymphocytes identified immunohistochemically within the biopsies. ICAM-1 was the most prominent CAM present on the endothelium of the normal nasal mucosa, with less expression of ELAM-1 and only minimal or absent expression of VCAM-1. In perennial rhinitis, both ICAM-1 (P less than 0.05) and VCAM-1 (P less than 0.01) expression on endothelial cells were increased and were positively correlated in their level of expression (P less than 0.002). The number of tissue LFA-1-positive cells was significantly greater (P less than 0.05) in the biopsies from the perennial rhinitics (median, 27.3/mm2) than from the healthy controls (median, 5.3 cells/mm2). LFA-1 expression significantly correlated with the number of ICAM-1-positive vessels (P less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of endothelial adhesion molecules in vivo. Increased endothelial ICAM-2 expression in lymphoid malignancies.

The authors have compared the reactivity of monoclonal antibodies (MAb) directed against endothelial adhesion molecules (ICAM-1, ICAM-2, VCAM-1, ELAM-1) in hyperplastic, nonmalignant, and malignant lymph nodes. The authors demonstrate that the reactivity with ICAM-1 MAb is stronger in the high endothelial venules (HEV) and other smaller vessels (SV) in lymphomas compared with hyperplastic lymph nodes. Similarly, the reactivity of an ICAM-2 MAb (6D5) was shown to be higher in malignant lymph nodes compared with nonmalignant ones. ICAM-2 MAb stained both the HEV and SV. VCAM-1 MAb reacted strongly with germinal centers and its endothelial reactivity was higher in the lymphoma nodes. ELAM-1 MAb stained only faintly some endothelial cells in malignant tissue. These data suggest that besides the known regulatable endothelial adhesion molecules ICAM-1 and VCAM-1, the expression of ICAM-2 can be modified.     

Expression of ICAM-1, VCAM-1 and ELAM-1 in angiofollicular lymph node hyperplasia (Castleman''s disease): evidence for dysplasia of follicular dendritic reticulum cells

The inducible adhesion molecules mediate important functions in the lymphoid tissues. We have investigated the expression of intercellular adhesion molecule 1 (ICAM-1), endothelial leucocyte adhesion molecule 1 (ELAM-1), vascular cell adhesion molecule 1 (VCAM-1), and platelet endothelial cell adhesion molecule (PECAM/CD31), using immunocytochemistry on cryostat sections of five lymph nodes from patients with Castleman's disease of the hyaline-vascular type. All five cases were characterized by marked hyperplasia of follicular dendritic reticulum cells, which were extensively present even in the mantle zone. Hyperplastic follicular dendritic reticulum cells showed marked expression of VCAM-1, and weak expression of ICAM-1. In two cases, several dysplastic giant cells with aberrant, polyploid nuclei showed aberrant expression of ELAM-1, an endothelium-restricted molecule. Dysplastic giant cells were positive with DRC-1 (an antibody to dendritic reticulum cells), VCAM-1 and occasionally ICAM-1, were negative for the endothelial cell markers factor VIII-related antigen and CD31 and were non-proliferating (Kl-67-). Cells positive for ICAM-1 or VCAM-1 were rare in the interfollicular areas. In all cases vascular hyperplasia was prominent, but endothelial cells were poorly activated in terms of expression of inducible adhesion molecules and of HLA-DR antigens. The possibility that dysplastic follicular dendritic reticulum cells have a pathogenetic role in Castleman's disease is discussed.     

Increased adhesion of human monocytes to IL-4-stimulated human venous endothelial cells via CD11/CD18, and very late antigen-4 (VLA-4)/vascular cell adhesion molecule-1 (VCAM-1)-dependent mechanisms.

Expression of adhesion molecules on endothelial cells (EC) can be up-regulated or induced by cytokines. The aim of the present study was to investigate the effect of IL-4 on both the expression of adhesion molecules on EC and monocyte adhesion to EC. Flow cytometric analysis showed that VCAM-1 expression on EC was up-regulated after stimulation with IL-4 for 24 h, whereas the expression of E-selectin (formerly called endothelial leucocyte adhesion molecule-1 (ELAM-1)) was not enhanced, and that of intercellular adhesion molecule-1 (ICAM-1) only slightly. The adhesion of monocytes to EC increased to maximum values upon stimulation of EC with IL-4 for 24 h. Coating of monocytes with MoAb against the integrin beta 2-subunit (CD18) significantly inhibited their adhesion to IL-4-stimulated EC; maximal inhibition was found when monocytes were coated with anti-CD18 MoAb in combination with MoAb against CD49d (the alpha-chain of VLA-4), whereas no inhibition was found when monocytes were coated only with MoAb against CD49d. Monocyte adhesion was not significantly inhibited when IL-4-stimulated EC were coated with MoAbs against ICAM-1 or VCAM-1 alone or in combination. Adhesion of monocytes was inhibited to a greater extent when in addition to coating of monocytes with MoAb against CD18 the EC were coated with MoAb against VCAM-1. From these results we conclude that monocytes bind to IL-4-stimulated EC via interaction of CD11/CD18 molecules on the monocytes with an as yet unknown endothelial ligand, and interaction of VLA-4 on monocytes with VCAM-1 on EC.     

Expression of ICAM-1, VCAM-1, E-selectin and TNF-alpha on the endothelium of femoral and iliac arteries in thromboangiitis obliterans

Immunohistochemical light and electron microscopical analysis of surgical biopsies obtained from femoral and iliac arteries of patients with thromboangiitis obliterans (TAO) were performed to investigate the presence of tumour necrosis factor-alpha (TNF-alpha) and expression of the endothelial cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Expression of ICAM-1, VCAM-1 and E-selectin was increased on endothelium and some inflammatory cells in the thickened intima in all TAO patients. Ultrastructural immunohistochemistry revealed contacts between mononuclear blood cells and ICAM-1-, and E-selectin-positive endothelial cells. These endothelial cells showed morphological signs of activation. The present data indicate that endothelial cells are activated in TAO and that vascular lesions are associated with TNF-alpha secretion by tissue-infiltrating inflammatory cells, ICAM-1-, VCAM-1- and E-selectin expression on endothelial cells and leukocyte adhesion via their ligands. The preferential expression of inducible adhesion molecules in microvessels and mononuclear inflammatory cells suggests that angiogenesis contributes to the persistence of the inflammatory process in TAO.     

Renal Expression of Adhesion Molecules in Anca-Associated Disease

INTRODUCTION: Anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated disease among other manifestations can underlie rapidly progressive glomerulonephritis (RPGN), with crescentic and necrotizing GN. Differences in pathogenic immune mechanisms in RPGN may provide differences in the renal expression of adhesion molecules mediating these lesions. METHODS: Renal intercellular adhesion molecule 1 (ICAM-1; CD54) and vascular cell adhesion molecule 1 (VCAM-1; CD106) were assessed in 40 patients with type I RPGN (anti-glomerular basement membrane antibodies, n = 4), type II (immune complexes, n = 17), and type III (ANCA, n = 19). Enzyme-linked immunosorbent assay (ELISA) for detection of immunoglobulin G antibodies against the Goodpasture's antigen and indirect immunofluorescence and ELISA for myeloperoxidase (MPO) and proteinase 3 (PR3) were performed for ANCA testing. Ten normal renal tissues were used as controls. Relationships between ICAM-1 and VCAM-1, histopathologic features, and CD18, CD14, and CD3 cells were analyzed. RESULTS: Abnormal ICAM-1 and VCAM-1 in tubule was seen in >80% of biopsies with RPGN. Abnormal VCAM-1 in glomerular tuft was seen in >60% of biopsies with RPGN. Glomerular ICAM-1 was associated with less glomerulosclerosis (chi (2) = 6.719, p = 0.01), less interstitial fibrosis (chi (2) = 4.322, p < 0.05), and less tubular atrophy (chi (2) = 8.547, p < 0.005). Glomerular VCAM-1 was associated with glomerular leukocyte infiltration (chi (2) = 4.698, p < 0.05). Glomerular tuft stains of ++/+++ for VCAM-1 was observed in 10% from MPO-ANCA-GN patients but in 60% from PR3-ANCA-GN (Fi = 8.538, p = 0.03). CONCLUSIONS: The following conclusions can be made from this study. (1) The renal expression of ICAM-1 and VCAM-1 is upregulated in RPGN, and this is associated with the histological activity. (2) De novo expression of VCAM-1 on glomerular tuft suggests that endothelial cells play a role in RPGN. (3) De novo tubular expression of ICAM-1 and VCAM-1 suggests that epithelial cells may participate in adhesive interactions in RPGN. (4) De novo expression of VCAM-1 at the glomerular tuft in PR3-ANCA positive patients seems greater than in MPO-ANCA positive patients, which suggests that testing specific immune activation mechanisms may play a role in ANCA-associated GN.