Recruitment of neutrophils in the local endotoxin response: association with de novo endothelial expression of endothelial leukocyte adhesion molecule-1.

Endothelium is central to the cellular infiltration that develops during inflammation, and a prominent feature of its involvement is the expression of adhesion molecules for circulating leukocytes. In the present study, we assessed the kinetics of endothelial adhesion molecule expression during the cutaneous endotoxin response in baboons. Immunostained cryostat sections and hematoxylin and eosin-stained paraffin sections of skin biopsies were examined using set scoring systems to provide semiquantitative data on the changes in endothelial phenotype and induced polymorphonuclear leucocyte (PMN) accumulation. Endothelium in control skin did not express endothelial leukocyte adhesion molecule (ELAM)-1 but did show a relatively weak expression of intercellular adhesion molecule (ICAM)-1. By 2 hours after injection of endotoxin (500 mcg of Escherichia coli-derived lipopolysaccharide), a marked expression of ELAM-1 developed that was associated with concurrent extensive adhesion and extravasation of PMN. The ELAM-1 expression subsequently decreased and was virtually absent by 9 hours. Mean scores for endothelial expression of ICAM-1 changed comparatively little over this time course, and mononuclear cell accumulation was minimal. The response to endotoxin differs from that to tumor necrosis factor injection; the latter causes sustained ELAM-1 expression, and delayed but pronounced increases in ICAM-1, with accompanying mononuclear cell extravasation. Thus, local endotoxin administration provides a model of acute inflammation in which PMN accumulation is associated with striking endothelial expression of ELAM-1. In this model, appreciable elevations in ICAM-1 expression are unnecessary for PMN infiltration.     

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.     

Modulation of adhesion molecule expression on endothelial cells during the late asthmatic reaction: role of macrophage-derived tumour necrosis factor-alpha.

In a previous work we have demonstrated that in patients exhibiting a late allergic reaction (LAR), alveolar macrophages (AM) collected 18 h after bronchial allergen challenge produced high levels of IL-6 and tumour necrosis factor-alpha (TNF) which is known to up-regulate the endothelial cell expression of adhesion molecules participating in the development of the inflammatory reaction in bronchial asthma. For these reasons, we evaluated the effect of AM supernatants from asthmatic patients developing an LAR on intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression by human endothelial cells. The expression of adhesion molecules was assessed by an ELISA method and compared with the effect of an optimal dose of human recombinant (hr) TNF. Results showed that AM supernatants, from challenged asthmatics developing an LAR, increased significantly the ICAM-1 and ELAM-1 expression on endothelial cells to a level similar to that obtained in the presence of hrTNF (500 U/ml) (P < 0.001 in both cases, respectively 90.4% and 75.2% of the level obtained with hrTNF). In contrast, AM supernatants from asthmatics at baseline or exhibiting, after challenge, a single early reaction had no significant effect on these parameters (P = NS in both cases, respectively 23.5% and 24.7% of the ICAM-1 expression, 22.7% and 15.3% of the ELAM-1 expression obtained with hrTNF). AM-derived TNF present in these supernatants was thought to play a key role in endothelial cell stimulation, since: (i) TNF concentration in AM supernatants correlated with its effect on ICAM-1 (r = 0.80, P < 10(-4)) and ELAM-1 expression (r = 0.88, P < 10(-5)); and (ii) a neutralizing anti-TNF antibody decreased their effect (68% and 80% respectively on ICAM-1 and ELAM-1 expression). Moreover, the role of IL-6 was excluded on the basis both of the hrIL-6 inefficiency to induce ICAM-1 and ELAM-1 synthesis, even in costimulation with hrTNF, and of anti-IL-6 antibody to neutralize the effect of AM supernatants. Our results suggest that, beside mast cells and lymphocytes, macrophages might participate in the induction of the local inflammatory reaction observed in bronchial asthma. During the LAR, cytokines and especially TNF are able, through an enhanced adhesion molecule expression on endothelial cells, to facilitate the bronchial cellular influx.     

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.     

Cytomegalovirus- and interferon-related effects on human endothelial cells Cytomegalovirus infection reduces upregulation of HLA class II antigen expression after treatment with interferon-γ

Cultured human umbilical vein endothelial cells (HUVEs) were infected with human cytomegalovirus (HCMV) strain AD169. Up to 50% HUVEs proved to be positive for HCMV early nuclear antigens 24 hours after inoculation with virus. Following infection kinetics of surface expression of HLA class I and II, intercellular adhesion molecule (ICAM-1) and endothelial lymphocyte adhesion molecule (ELAM-1) on HUVEs were investigated by means of flow cytometry. A slight increase in HLA class I expression was observed, whereas expression of HLA class II (DR, DP, DQ) antigens was not induced by infection with HCMV. Furthermore, when compared with uninfected cells treated with interferon-γ (IFN-γ), reduced enhancement of HLA-DR expression was conspicuous in HCMV-infected cells treated with IFN-γ. There is evidence that only a portion of HUVE is affected in its ability to upregulate HLA class II antigens. While expression of ICAM-1 was found to be enhanced between 8 and 20 hours after infection with a maximum at 12 hours after infection, no modulation of ELAM-1 was seen.     

Induction of E-selectin-dependent leukocyte recruitment by mast cell degranulation in human skin grafts transplanted on SCID mice.

Previous in vitro data indicate that degranulation of human mast cells triggers the induction of endothelial molecules important in leukocyte adhesion. In vivo experimental systems have not previously existed, however, to determine whether human mast cell degranulation is sufficient stimulus for leukocyte recruitment. To study this question, neonatal foreskins were transplanted onto immunodeficient mice. The grafts contained physiological numbers of human dermal mast cells that could be degranulated by a number of secretagogues that activate mast cells by different mechanisms. Degranulation was associated with an inflammatory response characterized by edema, up-regulation primarily of microvessel E-selectin, and influx of neutrophils. Leukocyte emigration associated with mast cell degranulation was inhibited by a monoclonal antibody against human E-selectin. These data indicate that degranulation of human mast cells in the human/SCID mouse model provokes cellular inflammation in skin. The ability to significantly inhibit early leukocyte infiltration with an antibody against E-selectin in this model supports the hypothesis that this molecule plays an important role in mast-cell-induced inflammation.     

Phospholipase C and perfringolysin O from Clostridium perfringens upregulate endothelial cell-leukocyte adherence molecule 1 and intercellular leukocyte adherence molecule 1 expression and induce interleukin-8 synthesis in cultured human umbilical vein endothelial cells.

Clostridium perfringens phospholipase C (PLC) and perfringolysin O (PFO) differentially induced human umbilical vein endothelial cell expression and synthesis of endothelial cell-leukocyte adherence molecule-1 (ELAM-1), intracellular leukocyte adherence molecule-1 (ICAM-1), and interleukin-8 (IL-8). PLC strongly induced expression of ELAM-1, ICAM-1, and IL-8, while PFO stimulated early ICAM-1 expression but did not promote ELAM-1 expression or IL-8 synthesis. PLC caused human umbilical vein endothelial cells to assume a fibroblastoid morphology, whereas PFO, in high concentrations or after prolonged low-dose toxin exposure, caused cell death. The toxin-induced expression of proadhesive and activational proteins and direct cytopathic effects may contribute to the leukostasis, vascular compromise, and capillary leak characteristics of C. perfringens gas gangrene.     

Vascular and nonvascular expression of INCAM-110. A target for mononuclear leukocyte adhesion in normal and inflamed human tissues.

Inducible cell adhesion molecule 110 (INCAM-110), is a 110-kd adhesion receptor for lymphocytes and monocytes identified on cytokine-activated endothelium. Using immunoperoxidase techniques, little or no INCAM-110 was detected on endothelium in normal human tissues. In contrast, INCAM-110 was expressed in postcapillary venules in a variety of active inflammatory processes. In acute appendicitis, INCAM-110 was found coincident with strong expression of endothelial leukocyte adhesion molecule 1 (ELAM-1), a cytokine-inducible molecule that functions in neutrophil adhesion. However, in certain chronic inflammatory processes (eg, sarcoidosis), INCAM-110 was observed without simultaneous ELAM-1 expression. Anti-INCAM-110 antibody E1/6 also marked several extravascular cell types, including lymphoid dendritic cells, some tissue macrophages, synovial lining cells, and reactive mesothelial cells. These data suggest a role for endothelial INCAM-110 in the pathophysiology of both acute and chronic inflammatory reactions. Furthermore INCAM-110 may function as an adhesion molecule for mononuclear leukocytes in a variety of extravascular sites.     

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.     

Expression patterns of leukocyte adhesion ligand molecules on human liver endothelia. Lack of ELAM-1 and CD62 inducibility on sinusoidal endothelia and distinct distribution of VCAM-1, ICAM-1, ICAM-2, and LFA-3.

Vascular expressed adhesion molecules mediate leukocyte reactivity and activation by receptor-ligand binding. A number of different ligand molecules have been identified to mediate the interaction between endothelial cells and leukocyte subpopulations. In this study, the tissue expression of ELAM-1, CD62 (PADGEM, GMP-140), VACM-1 (INCAM-110), ICAM-2, ICAM-1, and LFA-3 was analyzed on various liver endothelial cell types by immunohistology. The results reveal a differential expression of these molecules in normal liver and inflammation or rejection after liver transplantation. The selectins ELAM-1 and CD62 are basally expressed and inducible on portal tract endothelia (arterial and venous) and central vein endothelia with acute and chronic liver inflammation. Sinusoidal endothelia, however, lack this mechanism, even with severe inflammation, as in cases of irreversible rejection and sepsis. Portal and sinusoidal endothelia show a different expression and inducibility of VCAM-1, ICAM-1, ICAM-2, and LFA-3. The differences in expression of adhesion molecules on liver endothelial cell types may reflect their ability to regulate leukocyte trafficking and activation by means of the expression of specific ligand molecules. The inability of sinusoidal endothelia to express selectins may have implications for the pathophysiology of liver graft infiltration.     

Induction of mast cell interactions with blood vessel wall components by direct contact with intact T cells or T cell membranes in vitro

BACKGROUND: Mast cells exert profound pleiotropic effects on immune cell reactions at inflammatory sites, where they are most likely influenced not only by the extracellular matrix (ECM) and inflammatory mediators but also by the proximity of activated T lymphocytes. We recently reported that activated T cells induce mast cell degranulation with the release of TNF-alpha, and that this activation pathway is mediated by lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) binding. OBJECTIVE: To determine how this contact between the two cell types can modulate mast cell behaviour in an inflammatory milieu by examining the adhesion of mast cells to endothelial cells and ECM ligands in an integrin-dependent manner. METHODS: Human mast cells (HMC-1) were co-cultured with resting or activated T cells followed by testing their adhesion to endothelial cell and ECM ligands, stromal derived factor-1alpha (SDF-1alpha)-induced migration, and western blotting. RESULTS: Co-culturing HMC-1 with activated, but not with resting T cells resulted in marked stimulation of mast cell adhesion to vascular cell adhesion molecule-1 and ICAM-1 in a very late antigen-4- and LFA-1-dependent fashion. In addition, activated T cells or T cell membranes promoted HMC-1 adhesion to fibronectin (FN) and laminin. This effect was accompanied by the phosphorylation of extracellular regulated kinase and p38, but not of c-Jun N-terminal kinase. Importantly, the adhesive property of mast cells depended exclusively on the direct contact between the two cell types, since neither supernatants from activated T cells nor separation of the two cell populations with a porous membrane affected mast cell adhesion to FN. Furthermore, similar results were obtained when mast cells were incubated with purified membranes from activated T cells. These results suggest that, in addition to stimulating mast cell degranulation, the proximity of activated T lymphocytes to mast cells can mediate the adhesion of mast cell precursors to the endothelial ligands and ECM. Activated T cells also stimulated SDF-1alpha-induced mast cell migration. CONCLUSION: This symbiotic relationship between the two types of immune cells may serve to direct mast cells to specific sites of inflammation where their effector functions are required.     

Expression of intercellular adhesion molecule 1 (ICAM-1) on human articular cartilage chondrocytes.

Monoclonal antibodies have been used to demonstrate the induction of intercellular adhesion molecule 1 (ICAM-1) on chondrocytes in human articular cartilage. ICAM-1 was found not to be constitutively expressed but could be induced by exogenous interleukin 1 alpha(IL1- alpha) at concentrations ranging from 0.01 to 20 ng/ml during in vitro culture. Maximum expression was observed with 2-5ng/ml. In time-course experiments ICAM-1 was not expressed after 4h in culture with IL1 alpha. Expression was induced by 16h and was sustained for a minimum of 6 days in the continued presence of the cytokine. The endothelial leukocyte adhesion molecule (ELAM-1) was not expressed on chondrocytes and was not induced by IL1-alpha.     

Leukocyte traffic to sites of inflammation.

The adhesion of circulating leukocytes to the vascular endothelium is essential for effective host inflammatory and immune responses. Adhesion proteins expressed by both the leukocyte and endothelial cell have been well characterized, and studies of these molecules have shown that both cell types are actively involved in regulating these binding events. Most leukocyte (leukocyte integrins) and endothelial cell (vascular selectins, ICAM-1, and VCAM) adhesion proteins increase in expression and function in response to mediators released by inflamed tissues. In contrast, the expression and function of one type of leukocyte molecule, L-selectin (previously called LECAM-1, LAM-1, gp90MEL-14), is "down-regulated" by inflammatory signals. The purpose of this review is to summarize in vitro and in vivo regulatory and functional studies of some of the molecular mechanisms which regulate leukocyte-endothelial cell adhesion, with particular emphasis on L-selectin, and to present a hypothetical model of how these molecules may be orchestrated in vivo resulting in the control of host inflammatory responses.     

Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions.

Atherosclerotic lesions show features of a cell-mediated immune inflammatory process. From this viewpoint, the potential role of arterial endothelium in the recruitment of mononuclear cells (T lymphocytes and macrophages) was studied. The endothelium of diffuse intimal thickening (DIT) and atheromatous plaques (AP) in human coronary arteries and abdominal aortas was characterized for the expression of adhesion molecules ELAM-1, ICAM-1, and the major histocompatibility complex (MHC) class II antigens HLA-DR/DP. A marked increase in expression of ICAM-1 and ELAM-1, and to a lesser extent HLA-DR/DP was observed on endothelial cells that were adjacent to subendothelial infiltrates of T lymphocytes (CD3+, CD11a+, HLA-DR/DP+) and macrophages (CD14+, CD11a+, CD11c+, HLA-DR/DP+). This contrasted with a lower or absent expression of these activation markers at sites without prominent inflammatory cell infiltrates. These findings could be demonstrated in DIT as well as in AP. The observations suggest that cytokines produced by the subintimal infiltrates may activate the endothelium in a similar way as is observed in the microvasculature at sites of immune inflammation. The expression of these activation markers in the microvasculature is associated with enhanced leukocyte adhesion, permeability for macromolecules, and procoagulant activity, features known to occur also in early experimental atherosclerosis. The findings therefore support the concept that arterial endothelium plays an active role in the recruitment of mononuclear cells in atherosclerotic lesions.     

Cetirizine modulates adhesion molecule expression in a double-blind controlled study conducted in psoriatic patients

Psoriasis is a chronic inflammatory T-cell-mediated immune dermatosis, characterized by the cutaneous expression of adhesion molecules belonging to the beta1 and beta2 integrin subfamilies, such as intracellular adhesion molecule (ICAM)-1, ICAM-3, lymphocyte function associated antigen (LFA)-1, vascular cell adhesion molecule (VCAM)-1 and endothelial adhesion molecule (ELAM)-1. Cetirizine is a nonsedating, selective H1-receptor antagonist, whose therapeutic efficacy is probably the result of its effect on both the immediate allergic reaction and the late-phase allergic response. The aim of this study was to investigate adhesion molecule expression (ICAM-1, ICAM-3, VCAM-1, LFA-1 and ELAM-1) by using an immunophosphatase alkaline (APAAP) technique in a double-blind controlled study. Nineteen patients with active psoriasis vulgaris minima were randomized into two groups: group A (two men and six women, aged 22-59 years) was treated with cetirizine (30 mg a day, 3 times a day for 15 days) and group B (three men and eight women, aged 24-72 years) were administered placebo. Positive cells were counted by two independent and blinded observers and at least three adjacent high-power fields (250 X) were analyzed. In group A, ICAM-1-positive cells decreased from 75.8 (SE +/- 15.12) to 38.8 (SE +/- 7.57) ICAM-3-positive cells decreased from 61.7 (SE +/- 12.72) to 45.2 (SE +/- 9.44) and LFA-1 decreased from 103.9 (SE +/- 17.34) to 66.5 (SE +/- 8.63) after cetirizine treatment (p = 0.02). In group B, a nonsignificant reduction was found after placebo administration in the expression of adhesion molecules except for ELAM-1, which showed a slight variation, from 23.4 (SE +/- 3.56) to 21.5 (SE +/- 3.26). The reduction in the expression of adhesion molecules in psoriasis after cetirizine treatment suggests a possible inhibitory effect of this drug on some cell surface proteins and subsequently on the migration of inflammatory cells in psoriatic skin lesions. Our findings support its antiinflammatory effect in addition to its H1-blocking activity.     

ADHESION MOLECULES IN HUMAN CRESCENTIC GLOMERULONEPHRITIS

The expression of the intercellular adhesion molecule-1 (ICAM-1) and its ligand lymphocyte function associated antigen-1 (LFA-1 or αL), the vascular cell adhesion molecule-1 (VCAM-1), endothelial leukocyte adhesion molecule-1 (ELAM-1), and the cellular receptors for extracellular matrix, α 1, α 2, α 3, α 5, α 6, α V, β 1, and β3 integrin subunits, was studied in 28 patients with crescentic glomerulonephritis (GN) related to several mechanisms: four patients with anti-glomerular basement membrane antibodies or anti-GBM disease; 16 with immune complex mediated GN; and eight with pauci-immune GN, associated with vasculitis in four cases. A three-step immunoperoxidase technique was used on sections obtained from frozen renal biopsies. At the initial stage of evolution of the lesions, all the cells of the crescents expressed the β 1, β 3, α 1, α 3, and α V subunits of integrins, ICAM-1, and VCAM-1, and some cells expressed the α 2, α 5, α 6, and αL subunits of integrins along the plasma membrane. At a later stage, when the crescents were fibrocellular, α 3 and α1 subunit expression was polarized, localized mainly in front of the extracellular matrix. In fibrotic crescents, the α 2, α 5, α 6, and αL chains were no longer detected, and VCAM-1 and ICAM-1 expression was decreased. VCAM-1 and ELAM-1 appeared on endothelial cells of peritubular capillaries in relation to the appearance of infiltrating inflammatory cells. The results of this study show that several adhesion molecules were expressed on cells forming crescents and were modified during crescent evolution; that these molecules were up-regulated on endothelial cells in relation to the severity of the inflammatory response; and that whatever the mechanism of the glomerulonephritis, adhesion molecule expression was identical. It can be postulated that adhesion molecules play a role in crescentic glomerulonephritis. Better knowledge of these molecules in human glomerulonephritis may open the way to a new therapeutic approach.     

Adhesion molecule expression stimulated by Bacteroides thetaiotaomicron cell-surface antigens.

Bacteroides thetaiotaomicron, a Gram-negative anaerobic rod belonging to the Bacteroides fragilis group (BFG), is involved in many systemic and local, most frequently suppurative infections in man. The cell envelope of these rods is composed of two carbohydrate-containing antigens: lipopolysaccharide (LPS) and capsular polysaccharide (CPS). Adhesion molecules ICAM-1, VCAM-1 and E-selectin (ELAM-1) are induced on the endothelial cells by mediators of inflammation. The aim of this study was to assay the ability of B. thetaiotaomicron surface antigens to induce adhesion molecule expression on the endothelial cells. The influence of LPS and CPS on the expression of adhesion molecules on HMEC-1 cell line was examined in an ELISA test. ELISA was performed with monoclonal mouse anti-human: ICAM-1, VCAM-1 and E-selectin antibodies of the IgG class. B. thetaiotaomicron lipopolysaccharides revealed the ability to induce ICAM-1, VCAM-1 and E-selectin expression on the endothelial cells. Their activities were similar, but lower than the activity of Eschericha coli LPS. ICAM-1 was the most stimulated adhesion molecule. The strongest activation by LPS was achieved at the concentrations of 10.0 and 1.0 micrograms/ml. The ability of capsular polysaccharide to induce the expression of adhesion molecules was considerably weaker.     

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)