Expression of adhesion molecules in poststreptococcal glomerulonephrities

Because adhesion properties of leukocytes are important forthe influx and localization of leukocytes in sites of inflammation,we studied, the expression of intercellular adhesion molecule1 (ICAM-1), lymphocyte-function-associated antigen 1 (LFA-1),vascular cell adhesion molecule- I (VCAM-l) and CD 11b in 14kidney biopsies of PSGN patients, arbitrarily divided into earlybiopsies (less than 15 days after onset of PSGN) and late biopsies(17–90 days). In PSGN, intraglomerular ICAM-1 expressionwas increased in early biopsies (score 3.1 ±SEM 0.2;P<0.005) and decreased with time; in late biopsies the score(2.0±0.2) was similar to that of normal kidney (1.3±0.3).In the interstitium ICAM-1 was increased (early PSGN=836±56positive cells/mm² late=552±60.0; versus normal=364±12.4;P<0.05). LFA-l expressing cells in glomeruli were also increasedin early biopsies (10.0±2.1 positive cells per glomerularcross-section (gcs), versus normal 2.9±1.4; P<0.05).In the interstitium, LFA-1 positive cells were increased (earlyPSGN= 221±79.6 cells/mm² late PSGN=134.5±45.1,normal=21±8.7; P<0.05). VCAM-l in glomeruli and interstitiumwas not increased in PSGN. Our studies demonstrate increased expression of adhesion moleculesICAM-l and LFA-1 in the kidney of PSGN patients, and these findingswere more pronounced in early biopsies; adhesion molecules areprobably involved in the inflammatory infiltration of this disease.     

Circulating soluble adhesion molecules in systemic vasculitis

The plasma levels of soluble intercellular adhesion molecule-1(sICAM-1), E-selectin (sE-selectin), and vascular cell adhesionmolecule-1 (sVCAM-1), might reflect endothelial activation andinjury and would therefore be useful markers of disease activityin vasculitis. To investigate this we measured the levels ofsICAM-1, sE-selectin, and sVCAM-1 by two-site ELISAs in theplasma of patients with (a) active vasculitis (n = 16), (b)vasculitis in remission (n = 15), (c) chronic renal failure(CRF) (n = 10), and (d) normal healthy controls (n = 10). PlasmasICAM-1 levels were significantly higher in patients with activevasculitis, 323 ng/ml (193–607) compared with patientswith inactive vasculitis, 199 ng/ml (131–297); P = 0.0006and healthy controls, 188 ng/ml (138–259); P =0.0002.Plasma sE-selectin levels were also significantly higher inthe patients with active vasculitis, 45 ng/ml (15–65)compared with patients with inactive vasculitis, 25 ng7sol;ml(15–55); P=0.027 but not when compared with healthy controls,35 ng/ml (20–55); P=0.16. There was no difference in plasmasVCAM-1 levels between patients with active vasculitis, OD 0.56(0.45–0.85) and inactive disease, OD 0.58 (0.47–0.79)(P=0.12) or with healthy controls OD 0.49 (0.42–0.68)(P=0.48). There were no significant differences between theplasma levels of any of the soluble adhe sion molecules betweenpatients with active vasculitis and patients with chronic failure.In patients with a vasculitis there was a significant correlationbetween sICAM-1 and plasma C-reactive protein (CRP) (r=0.60,P=<0.01) and plasma von Willebrand factor (vWF) (r=0.42,P<0.05). Likewise there was a cor relation between sE-selectinand CRP (r=0.45, P<0.02) but not with vWF. There was a significantcorrelation between sICAM-1 and sE-selectin (r=0.38, P<0.05),but not between sICAM-1 and sVCAM-1 or sE- selectin and sVCAM-1.No correlation was found between sVCAM-1 levels and CRP andvWF concentrations or between the levels of any of the solubleadhesion molecules and serum creatinine. Plasma levels of sICAM-iand of sE-selectin but not of sVCAM-1 reflect disease activityin vasculitis and may be markers of endothelial and or tissueinjury in these disorders.     

Localization of adhesion molecules on human spermatozoa by fluorescence microscopy

Summary.  The expression of adhesion molecules on human spermatozoa of healthy probands was analysed. The localization patterns of adhesion molecules (AM) on the spermatozoal surface were documented by fluorescence microscopy. Spermatozoa were incubated with antibodies against α1 (CD49a), α2 (CD49b), α3 (CD49c), α4 (CD49d), α5 (CD49e), α6 (CD49f) chains of β1 integrins, β1 (CD29), β2 (CD18), αV (CD51), β3 (CD61) and β4 integrin chains, the LFA-3 (Lymphocyte function antigen, CD58) from the immunoglobulin superfamily and the extracellular matrix proteins laminin, fibronectin and collagen IV. For collagen IV, α1 and α2 chains no expression could be noticed. Laminin was detected at the acrosomal membrane, fibronectin and β4 chain mainly at the equatorial membrane. The fibronectin receptors α3, α4 and α5 chains of the β1 integrins were mainly located on acrosomal and equatorial membrane areas. Laminin receptor α6 chain was located postacrosomal and less frequently acrosomal. β2 chain and vitronectin receptors αV and β3 chains had a mainly postacrosomal localization pattern. LFA-3 was found constantly on postacrosomal membrane areas. Double staining technique was used to prove the simultaneous occurrence of fibronectin and its integrin receptors α3, α4 and α5 chains and of αV and β2 chains on spermatozoa. The localization patterns of integrins on double stained spermatozoa were similar to the patterns described for single stained spermatozoa. The localization of fibronectin appeared to be influenced by the presence of integrins: the typical equatorial fibronectin band disappeared in case of an equatorial localization of integrins.     

Changes in the expression of adhesion molecules as peripheral blood monocytes differentiate into peritoneal macrophages

Peritoneal macrophages, derived from peripheral blood monocytes,are the chief cellular defenders against invasion of the peritonealcavity by infectious organisms. Monocyte migration into theperitoneal cavity depends upon a coordinated series of adhesiveevents, utilizing cell surface receptors known as adhesion molecules.in order to better understand the mechanisms of leucocyte infiltrationof the peritoneum during peritonitis, we studied the relativeexpression of adhesion molecules on monocytes and peritonealmacrophages from patients on continuous ambulatory peritonealdialysis (CAPD). Peripheral blood and spent peritoneal dialysisfluid were obtained from patients undergoing CAPD, and the levelof expression of various adhesion molecules on the monocytes/macrophagesanalysed by flow cytometry using receptor-specific monoclonalantibodies. Monocytes were also purified from the peripheralblood of volunteer donors, cultured in vitro for varying periods,and analysed in the same manner. Consistent differences in expressionof certain adhesion molecules were found between monocytes andperitoneal macrophages, and similar changes occurred on monocytescultured in vitro. Concurrent infection had no clear effect.Several receptors (integrins 4ß1 6ß1, Lß₂;and IIbß3, and platelet endothelial cell adhesionmolecule-1) were significantly decreased on peritoneal macrophages,while only the integrin vß5 increased. It is concludedthat monocyte differentiation into peritoneal macrophages isaccompanied by characteristic alterations in the adhesion moleculerepertoire on the cell surface, emphasizing the different adhesiverequirements of these two cell types.     

Expression of adhesion molecules and RANTES in kidney transplant from nonheart-beating donors

The main difference between cadaveric kidneys from donors with a heartbeat (HBD) and kidneys from nonheart-beating donors (NHBD) is related to warm ischemia/reperfusion time which constitutes an acute inflammatory process. On the contrary, brain death induces in HBD expression of pro-inflammatory adhesion molecules, making it important to evaluate this kind of molecules in both types of donors. Human renal biopsies from NHBD, HBD and normal kidneys (ischemia time = 0) were taken and frozen just before transplant. A semi-quantitative RT-PCR method was used to determine intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), lymphocyte function associated antigen (LFA-1), LFA-3, CD40, CD40 ligand (CD40L) and RANTES (regulated upon activation, normal T-cell expressed and secreted) gene expression. We have detected an elevated relative gene expression of ICAM-1, VCAM-1 and RANTES in NHBD biopsies compared with normal kidneys. In the case of RANTES, the gene expression from NHBD biopsies was higher than observed in HBD biopsies. The rest of genes were not augmented in any group. Preliminary data about early outcome of transplants indicates a correlation between pretransplant RANTES high gene expression levels and early post-transplant acute rejection. The gene expression of pro-inflammatory molecules like adhesion molecules and RANTES is augmented in kidneys from cadaveric NBD just before transplant. The expression is higher probably because of the prolonged warm ischemia period. A larger clinical study is necessary to clarify the effects of these variable expressions on the transplant outcome.     

Circulating soluble adhesion molecules in ANCA-associated vasculitis.

BACKGROUND: To evaluate whether changes in concentrations of soluble (s) E-selectin, sP-selectin, sL-selectin, intercellular adhesion molecule 1 (sICAM-1), and vascular cell adhesion molecule 1 (sVCAM-1) reflect disease activity in patients with ANCA-associated vasculitis and whether serum levels of these adhesion molecules are related to the degree of renal failure in patients with chronic renal failure (CRF). SUBJECTS AND METHODS: A sandwich ELISA was used to measure these soluble adhesion molecules in (i) sera from 20 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (10 patients with Wegener's granulomatosis (WG) and 10 patients with microscopic polyangiitis (MPA)), obtained at the time of diagnosis and during the remission period; (ii) sera from 40 patients with CRF not undergoing haemodialysis. RESULTS: At the time of diagnosis, serum levels of sE-selectin, sICAM-1 and sVCAM-1 (88+/-42 ng/ml, 437+/-184 ng/ml, 1720+/-1174 ng/ml respectively) were significantly higher in patients with ANCA-associated vasculitis than in healthy controls (P<0.0001, P=0.002 and P=0.001 respectively). Serum sP-selectin values did not differ from those obtained in normal donors. In contrast, sL-selectin levels (940+/-349 ng/ml) were significantly lower in patients than those recorded in healthy controls (P<0.0001). A significant decrease in concentrations of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 was observed between active and remission phases (P<0.0001, P=0.002, P=0.001 and P=0.001 respectively). No significant differences were observed in sL-selectin levels between active and remission phases. sL-selectin concentrations (802+/-306 ng/ml) during the remission phase remained lower than those observed in healthy controls (P<0.0001). No correlation was observed between serum creatinine and sE-selectin, sP-selectin, sICAM-1 and sVCAM-1 in patients of the CRF group. A slight negative correlation was established between creatinine and sL-selectin concentration. CONCLUSIONS: Increased serum levels of sE-selectin, sICAM-1, and sVCAM-1 and decreased levels of sL-selectin in active ANCA-associated vasculitis, and the normalization of sE-selectin, sICAM-1, and sVCAM-1 during the remission phase suggest that the concentration of soluble levels of these adhesion molecules reflects disease activity. The decrease in sP-selectin levels between active and inactive phases also suggest that this receptor may reflect clinical activity. The lack of correlation between serum levels of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 and the degree of renal failure in patients with CRF suggests that the mechanism of clearance of these molecules is not renal.     

Antibodies to human adhesion molecules and their ligands: Cross-species reactivity and potential application in xenotransplantation

Abstract: Given the renewed interest in the possibility of using animals as an alternative source of organs for transplantation, it would be useful to have tools to study and manipulate the inflammatory response to a xenograft. With this in mind, we have screened cynomolgus monkey and porcine tissue with 37 antibodies specific for human leukocyte differentiation antigens and adhesion molecules. The cynomolgus monkey, an old world primate, is a concordant species with respect to humans, in contrast to the pig, which is a discordant species. The cross-species reactivities of the antibodies tested fall into three groups: i) no crossreactivity; ii) crossreactivity with a tissue distribution similar to that in the human; iii) crossreactivity, but with a distribution different from that in the human. Those antibodies directed against E- and P-selectin, ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1), which were reactive with monkey tissue, had a similar distribution to that seen in human tissue, but were unreactive with the porcine tissue tested. While an anti-CD31 antibody detected a conserved epitope on endothelium, species differences were apparent in leukocyte reactivity. One of the antibodies directed against CD 18 reacted with leukocytes in all three species, whereas the other antibody detected an epitope present on porcine muscle/connective tissue. While antibodies to VLA-4 (Very Late Antigen-4) detected a small number of leukocytes in the kidney, they also reacted with the Bowman's capsule in the kidney and matrix protein/connective tissue in the lymph node. This study indicates that when antibodies react across species, some epitopes recognized in the old world nonhuman primates may have a distribution similar to those detected in human tissue, whereas in more distant species such as the pig, in many instances the epitope is present on entirely different structures. Nevertheless, the absence of crossreactivity of human reagents with porcine tissue may allow targeting of molecules in a species-specific manner, allowing their use for diagnostic or therapeutic purposes.     

The expression of cell adhesion molecules,cadherins: markers of kidney morphogenesis

Cadherins are protein molecules that promote cell adhesion in the presence of calcium. There are several classes of cadherins. The expression of two of these, namely the N- and E-cadherins, is intrinsically associated with the embryonic development of the kidney and thus their study provides a molecular basis for understanding the epithelial organization of this organ.     

细胞粘附分子选择素CD62 P在胃癌中的表达及其意义

目的探讨细胞粘附分子ＣＤ６２Ｐ（Ｐ选择素）在胃癌的表达及与其生物学行为的关系，并进行临床病理学评价。方法采用免疫组化方法（ＳＰ法）观察了ＣＤ６２Ｐ在６８例胃癌原发灶中的表达情况，对胃癌标本进行系统病理学检查。结果非癌胃组织未见ＣＤ６２Ｐ表达，胃癌组织中ＣＤ６２Ｐ表达阳性率为５６％（３８／６８）。阳性表达在癌组织血管内皮细胞上，部分癌细胞也可见ＣＤ６２Ｐ表达。在浸透浆膜（Ｔ３、Ｔ４）、淋巴结转移数超过５个、转移率大于５０％、转移至Ⅱ站以远及Ⅲ、Ⅳ期胃癌ＣＤ６２Ｐ表达显著增强（Ｐ＜００５）。结论ＣＤ６２Ｐ与胃癌的生物学行为密切相关，其表达的检测对评估胃癌淋巴结转移程度和分析病期可能有一定价值。     

FK778, a novel immunosuppressive agent, reduces early adhesion molecule up-regulation and prolongs cardiac allograft survival.

The adhesion molecules, P-selectin, ICAM-1, and VCAM-1 are important mediators of T-cell adhesion and T-cell co-stimulation. We investigated the effect of the malononitrilamide FK778 on cardiac allograft survival, acute allograft rejection, and adhesion molecule up-regulation in a heterotopic, cardiac transplantation model. Rats received low- or high-dose FK778 or no treatment. Grafts were harvested on the fifth postoperative day for histologic examinations. To assess allograft survival, recipients were treated for a maximum of 10 days and grafts were harvested after cessation of the contractile activity. FK778 low dose showed a mild but significant decrease in mononuclear infiltration but failed to markedly reduce histologic rejection, adhesion molecule up-regulation, or to prolong allograft survival. However, high-dose FK778 treatment significantly reduced early up-regulation of P-selectin, ICAM-1, and VCAM-1, abolished infiltration, reduced histologic rejection and resulted in prolonged cardiac allograft survival. Therefore, FK778 is a novel, highly desirable immunosuppressive drug for transplantation medicine.     

Expression of cell adhesion molecules in an established and characterized new human renal cell cancer line,CCF-RC7

In order to investigate the importance of cell adhesion molecules (CAMs) in renal cell carcinoma (RCC), a cell line, designated as CCF-RC7, was established from a human RCC of the clear cell type. CCF-RC7 was passaged over 50 times in vitro for 31/2 years. The cell line has an epithelial morphology and a doubling time of 30 h, forming colonies in soft agar with an average efficiency of 10.4% and producing clear cell tumors in athymic nude mice. CCF-RC7 cells have an aneuploid-hypotetraploid karyotype with a modal chromosome number of 82 and rearrangements in chromosomes 9, 12 and 14. Immunohistochemical and flow immunocytometric analyses revealed high expression of ICAM-1 (CD54), and Hermes antigen (CD44), which was significantly upregulated by cytokine and PMA treatment. VLA-4 was expressed on approximately 20% of tumor cells and could not be altered by cytokine or PMA stimulation. High expression of sialyl Lewis X was also demonstrated by immunohistological examination. This newly characterized cell line will serve as a useful model for the study of CAMs during hematogenous metastasis and host defense mechanisms in human RCC.     

Influence of intraperitoneal application of taurolidine/heparin on expression of adhesion molecules and colon cancer in rats undergoing laparoscopy

BACKGROUND: Recent experimental studies have shown that intraperitoneal administration of taurolidine/heparin causes a reduction of local tumor growth after laparoscopy in rat models. It might be that the anti-adherent activities of these agents are responsible for this effect. In this study we investigated the adhesion molecules E-cadherin, beta1-integrin, and CD44. MATERIALS AND METHODS: Following a 10,000 colon adenocarcinoma cells' (DHD/K12/TRb) intraperitoneal application a cecum resection and a partial parietal peritoneum resection (1 x 1 cm) were performed using a three trocar technique in 30 BD IX rats. After randomization in two groups, the cecum suture line and the parietal peritoneal defect were either lavaged with 1 mL of 0.5% taurolidine/10 IU heparin or with equal amounts of 0.9% normal saline solution. Rats were sacrificed four weeks after operation and total tumor growth was determined. E-cadherin, beta1-integrin, and CD44 were assessed immunohistochemically on the tumor tissue. RESULTS: The expression of E-cadherin was significantly reduced to 46.7% (complete loss of staining) in the taurolidine/heparin group. Although no significant difference was detected concerning the beta1-integrin and CD44 expression, a slightly reduced expression level with 26.7% of negative staining in metastases of the taurolidine/heparin group was observed. The total tumor weight (171.1 +/- 181.2 mg) as well as the total number of tumor lesions was also reduced by the substances compared to the control group (283.2 +/- 91.4 mg). CONCLUSIONS: Taurolidine/heparin led to a significant reduction of local tumor growth. Additionally a reduction of the expression of E-cadherin was observed. However, the biological behavior of this molecule is multivariant, controversial and still unclear. Further studies should elucidate its role in the epithelial tumor genesis.     

连接粘连分子3对肾癌细胞迁徙和凋亡的作用机制

目的研究连接粘附分子3(JAM3)在肾癌细胞中的表达情况以及在调控肾癌细胞迁徙和凋亡过程中的可能作用及机制。方法①RT-qPCR和Western-blot检测JAM3的表达水平;②siRNA、流式细胞仪、细胞划痕实验及细胞迁移实验分析其对RCC迁移和凋亡的影响;③Western-blot检测E-钙粘蛋白、N-钙粘蛋白、整合素β1和基质金属蛋白酶2(MMP-2)表达水平,初步探究JAM3影响癌细胞迁移的可能机制。结果①与正常肾小管上皮细胞相比,人肾癌细胞中的JAM3表达显著上调(P<0.05);②JAM3敲除可促进肾癌细胞的凋亡(P<0.05)及抑制肾癌细胞迁移(P<0.05);③JAM3基因敲除后,肾癌细胞中E-粘连蛋白的表达增加,N-粘连蛋白、整合素β1、MMP-2、Bcl-2的蛋白水平下降(P<0.05)。结论 RCC中JAM3表达上调,并可能通过调控E-钙粘蛋白、N-钙粘蛋白、整合素β1、MMP-2表达水平抑制癌细胞凋亡和促进其迁移。     

Impact of adhesion molecules of the selectin family on liver microcirculation at reperfusion following cold ischemia

We investigated the role of adhesion molecules in the early phase of reperfusion following cold ischemia. Livers of male Lewis rats were preserved for 0 h (group A) or 24 h in University of Wisconsin (UW) solution without additives (group B) or in UW solution with anti-ICAM-1 antibody (group C) or anti-E-selectin-1, SLe^x and SLe^a antibodies (group D). The livers were then reperfused with diluted rat whole blood (DWB; groups A and B), DWB containing anti-ICAM-1 and LFA-1 antibodies (group C) or DWB containing anti-L-selectin, SLe^x and SLe^a antibodies (group D). The reperfusion was perfomed at 37°C for 1 h at 5 cm H₂O of perfusion pressure. During reperfusion, hepatic microcirculation was assessed by monitoring portal and peripheral tissue blood flow. Bile production was significantly reduced in group B livers compared with those in group A. Anti-ICAM-1 and LFA-1 antibodies failed to improve hepatic microcirculation, whereas anti-LECAM-1, SLe^x and SLe^a antibodies significantly improved the microcirculation. Bile production in group C and D livers was comparable to that in group B livers. Preservation for 24 h significantly increased the release of TNF- from 0.207 to 43.7 pg/g per hour during reperfusion. Monoclonal antibodies to the adhesion molecules did not suppress the release of TNF- in groups C and D. Histological examination demonstrated a lack of leukocyte infiltration or thrombus in hetapic microvessels. The extent of hepatocyte necrosis did not differ among groups B, C, and D. We conclude that the microcirculatory disturbance in the early phase of reperfusion occurs as a result of the tethering of leukocytes through the interaction of the selectin family and their ligands, and that the ICAM-1-LFA-1 pathway is not involved in this step. The lack of improvement in bile production with antibodies to the selectin family and their ligands strongly suggests that other mechanisms participate in the deterioration of hepatic function.     

Identification of swine and primate cellular adhesion molecules (CAM) using mouse anti-human monoclonal antibodies

Abstract: A series of adhesion molecules of swine and Cynomolgus monkeys were identified by screening for cross-reactivity with a panel of monoclonal murine anti-human adhesion molecule antibodies obtained from the 5th International Workshop and Conference on Human Leukocyte Differentiation Antigens (Boston, MA, USA, 1993). Of 162 antibodies tested, 25 were found that cross-react significantly with swine cells, while 67 were found to react strongly with cells of Cynomolgus monkeys. Cross reactivities to swine were found with antibodies to CD 18 (β2 integrin), CD29 (β1 integrin), β7 integrin, CD49d (α4 integrin) CD49b(α2 integrin), and to a lesser extent to CD62p(P-selectin), CD62L(L-selectin), CD102(ICAM-2), CD11b, and CD49c (α3 integrin). Cross-reactivities to primate cells also included CD18, CD29, CD49d, and CD49b. In addition, reactivities to Cynomolgus monkey cells were detected with antibodies to CD11 (a, b, and c), CD31, CD44, CD49e, CD49f, CD50, CD54, CD56, CD62p, CD 102 and CD56. The tissue distribution and molecular weight of the swine antigens are similar to their human counterparts. These findings provide a spectrum of monoclonal antibodies that react with shared epitopes on homologous adhesion molecules of human, swine, and monkey cells, thus facilitating study of the role of these molecules in the immunobiology of monkeys and swine. These reagents may be useful to dissect the role of adhesion molecules in both alio- and xenoreactivity.     

Soluble adhesion molecules in end-stage renal disease: a predictor of outcome.

BACKGROUND: Inflammation is thought to contribute to initiation and aggravation of atherosclerosis through a process predominantly mediated by adhesion molecules. The aims of this study were to investigate the association between the concentrations of circulating soluble intercellular (sICAM-1) and vascular cellular (sVCAM-1) adhesion molecules and clinical outcome, and to evaluate the effect of antihypertensive drugs on sICAM-1 and sVCAM-1 concentrations in end-stage renal disease (ESRD) patients. METHODS: We prospectively investigated 310 (191 males) incident ESRD patients, 53+/-12 years old, shortly before the start of renal replacement therapy. Glomerular filtration rate (GFR) was 6.4 (range 0.8-16.5) ml/min/1.73 m(2). Plasma sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) kits. Survival was determined from the day of examination, with a mean follow-up period of 39 (range 1-123) months. RESULTS: In non-adjusted analysis, high sICAM-1 and sVCAM-1 levels were associated with all-cause and cardiovascular (P<0.001) mortality. After adjusting for age, gender, diabetes mellitus, serum cholesterol, C-reactive protein (CRP), subjective global assessment and angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB), the association between high sICAM-1 and mortality remained significant for all-cause (HR 1.9; CI 1.2-2.9, P = 0.004) and cardiovascular (HR 1.8; CI 1.1-3.1, P = 0.02) mortality, and a high sVCAM-1 was associated with all-cause mortality (HR 1.7; CI 1.04-2.7, P = 0.03). Furthermore, the concentration of sICAM-1, but not sVCAM-1, was lower in patients receiving ACEI/ARB (254+/-83 vs 275+/-92 ng/ml; P<0.05) or patients receiving calcium channel blockers (CCB, 251+/-75 vs 273+/-95 ng/ml; P<0.05) than in non-users. CONCLUSIONS: In ESRD patients, sICAM-1 and sVCAM-1 are independent predictors of all cause and cardiovascular death. The use of ACEI/ARB or CCB was associated with decreased concentrations of soluble adhesion molecules.     

C5b-9 and adhesion molecules in human idiopathic membranous nephropathy.

BACKGROUND: Cellular immune responses and C5b-9 seem to play an important role in the pathogenesis and progression of idiopathic membranous nephropathy (IMN). The aim of the study was to investigate the role of C5b-9 and adhesion molecules in the pathogenesis of the disease. METHODS: The clinical and pathological data of 35 patients with biopsy-proven IMN were correlated with immunohistochemical findings using monoclonal antibodies against T lymphocytes, monocytes/macrophages (MM), HLA-DR antigens, C5b-9, and adhesion molecules such as alpha3beta1, LFA-1beta, and ICAM-1. RESULTS: In the glomeruli, C5b-9 deposits showed a significant correlation with the intensity of IgG and C3 deposition. The stage of the disease had a significant negative relationship with the glomerular alpha3beta1 expression. In the tubulointerstitium (TIN), the number of HLA-DR(+) cells was highly correlated with the numbers of total T lymphocytes, MM, and LFA-1beta(+) cells, as well as with the percentage of tubules with C5b-9 deposits. The extent of ICAM-1 expression in the TIN was significantly correlated with the numbers of interstitial MM, HLA-DR(+), and LFA-1beta(+) cells, as well as with the extent of tubular C5b-9 deposition. The severity of tubular atrophy and interstitial fibrosis had a relationship with the numbers of total T lymphocytes, MM, HLA-DR(+), and LFA-1beta(+) cells and with the extent of tubular C5b-9 deposition and ICAM-1 expression in the TIN. Serum creatinine (Scr) was highly correlated with the numbers of interstitial total T lymphocytes, MM, HLA-DR(+), and LFA-1beta(+) cells. Moreover, Scr had a significant relationship with the severity of tubular atrophy and interstitial fibrosis, as well as with the extent of tubular C5b-9 deposition and ICAM-1 expression in the TIN. Proteinuria was significantly correlated with the extent of tubular alpha3beta1 expression. CONCLUSIONS: In IMN, C5b-9 formation may be secondary to IgG and C3 deposition. Proteinuria may contribute to the TIN damage by altering the expression of alpha3beta1 integrins in tubular cells. De novo ICAM-1 and C5b-9 expression within the TIN as well as the activated interstitial cells may be important factors leading to renal damage and renal function impairment.     

急性胰腺炎胰腺血液流变学改变与细胞粘附分子的表达

目的　探索急性胰腺炎 (AP)实验动物模型的早期胰腺局部血液流变学改变、流体切应力作用下中性粒细胞表面粘附分子表达在AP发展中的作用。　方法　将 2 1只Wistar大鼠随机分为3组 ,用蛙皮缩胆囊肽 (caeralein)诱发AP动物模型 ,用Low shear 30血流流变仪检测全血表观粘度 ,用流式细胞仪分析切应力介导的中性粒细胞表面粘附分子的表达。　结果　 (1)各实验组血清淀粉酶升高 ,与正常组相比 ,差异有显著性 (t=6 9 0 2 9,t =79 734,P <0 0 5 )。 (2 )不同切变率下各实验组的全血表观粘度均增高 ,尤以低切变率下增高更为显著 (0 5 12s-1:t=10 72 5 ,t=16 94 5 ;5 96s-1:t=12 781,t=11 992 ,P <0 0 5 )。 (3)在切变率作用下各组CD18的表达随着切变率的升高而增加 ,且在切变率为 94 5s-1和 12 8 5s-1时 ,有显著性差异 (94 5s-1:t=7 4 0 3,t=13 32 3,t=16 6 5 5 ;12 8 5s-1:t=10 0 92 ,t=2 8 5 31,t=2 4 5 6 3,P <0 0 5 )。 (4)低切变率作用对不同组别CD 6 2L的表达无显著影响 ,当切变率升高≥ 94 5s-1时 ,各组CD 6 2L的表达开始下调 ,差异有显著性 (94 5s-1:t=10 6 87,t=19 376 ,t=12 84 8;12 8 5s-1:t=2 6 15 2 ,t=4 8 4 0 2 ,t=5 6 814 ,P <0 0 5 )。　结论　AP早期胰腺微循环全血表观粘     

利多卡因抑制内皮细胞粘附因子表达进而抑制肝癌细胞粘附脐带静脉内皮细胞

【摘要】 目的 探讨利多卡因对血管内皮细胞粘附因子表达的影响。方法 采用不同浓度利多卡因预处理脐带静脉内皮细胞（HUVECs）30 min后,加入肿瘤坏死因子α（TNFα）进行刺激。通过实时荧光定量聚合酶链反应检测选择素E（CD62E）、血管细胞粘附分子-1（VCAM-1）和细胞间粘附分子-1（ICAM-1）表达量,蛋白免疫印迹分析NF-Kappa B（NF-κB）通路蛋白的改变,并通过细胞粘附实验评估利多卡因预处理对肝癌细胞（HepG2）粘附于HUVECs的影响。结果 利多卡因预处理可以明显抑制p65并抑制HepG2粘附于HUVECs。qRT-PCR结果表明利多卡因预处理可明显抑制TNF-α刺激后的CD62E、VCAM-1和ICAM-1表达水平的增高。结论 利多卡因可能通过抑制NF-κB通路进而抑制细胞粘附因子表达并抑制结肝癌细胞粘附于血管内皮细胞。