Distribution Of Cell Adhesion Molecules Research Articles

Glia trigger endocytic clearance of axonal proteins to promote rodent myelination

Axons undergo striking changes in their content and distribution of cell adhesion molecules (CAMs) and ion channels during myelination that underlies the switch from continuous to saltatory conduction. These changes include the removal of a large cohort of uniformly distributed CAMs that mediate initial axon-Schwann cell interactions and their replacement by a subset of CAMs that mediate domain-specific interactions of myelinated fibers. Here, using rodent models, we examine the mechanisms and significance of this removal of axonal CAMs. We show that Schwann cells just prior to myelination locally activate clathrin-mediated endocytosis (CME) in axons, thereby driving clearance of a broad array of axonal CAMs. CAMs engineeredto resist endocytosis are persistently expressed along the axon and delay both PNS and CNS myelination. Thus, glia non-autonomously activate CME in axons to downregulate axonal CAMs and presumptively axo-glial adhesion. This promotes the transition from ensheathment to myelination while simultaneously sculpting the formation of axonal domains.

Expression of cell adhesion molecule 1 in gastric neck and base glandular cells: Possible involvement in peritoneal dissemination of signet ring cells

AimsTo determine cellular distribution of cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, in the human oxyntic gastric mucosa, and to explore possible involvement in the development and peritoneal dissemination of signet ring cell (SRC) gastric carcinoma, which often develops in the oxyntic mucosa. Main methodsImmunohistochemistry and double immunofluorescence were conducted on surgical specimens of normal and SRC-bearing stomachs and peritoneal metastatic foci of SRCs. KATO-III (lacking CADM1) and HSC-43 (expressing CADM1) SRC cell lines were cocultured on a Met-5A mesothelial or TIG-1 fibroblastic cell monolayer. Key findingsIn the oxyntic gland, some neck and nearly all base glandular cells were CADM1-positive, and mucin 5AC-positive cells were CADM1-negative, while some mucin 6-positive neck cells were CADM1-positive. Foveolar-epithelial, parietal, and endocrine cells were CADM1-negative. CADM1 was negative in all SRC carcinomas that were confined within the submucosa (n = 11) and all but one of those invading deeper (n = 15). In contrast, peritoneal metastatic foci of SRCs were CADM1-positive in five out of eleven cases (P < 0.01). In the cocultures, exogenous CADM1 made KATO-III cells adhere more and grow faster on a Met-5A monolayer, not on TIG-1 monolayers. HSC-43 cells adhered more and grew faster on Met-5A than on TIG-1 monolayers, which were partly counteracted by a function-neutralizing anti-CADM1 antibody. SignificanceNearly all chief cells and a part of mucous neck cells express CADM1. SRC gastric carcinoma appears to emerge as a CADM1-negative tumor, but CADM1 may help SRCs develop peritoneal dissemination through promoting their adhesion and growth in the serosal tissue.

Spatial distribution of cell adhesion molecules on the peritoneal surface in the cecal perforation-induced peritonitis.

For understanding the immunological functions of the peritoneum, spatial localization of integrins and their ligands was studied by immuno-SEM on the peritoneal surface of mice with cecal perforation-induced peritonitis. The cecal peritoneum 24 hr after perforation was stained with specific antibodies against LFA-1, Mac-1, VLA-4, ICAM-1, VCAM-1, and fibronectin diluted with cold University of Wisconsin (UW) solution in conjunction with immuno-gold labeling. The spatial localization of those cell adhesion molecules was detected by backscatter electron (BSE) imaging with field emission scanning electron microscope (FESEM). Numerous leukocytes with diverse surface ultrastructure were observed on the peritoneal surface by FESEM. Some leukocytes were in contact with mesothelial cells, and others adhered to the exposed underlying connective tissue. The BSE imaging showed the ubiquitous distribution of Mac-1 on all membrane domains of leukocytes, i.e., cell body, ruffles, and microvilli. In contrast, predominant expressions of LFA-1 and VLA-4 were discernible on ruffles/microvilli of some leukocytes. The mesothelial cells remaining in the inflamed area expressed both ICAM-1 and VCAM-1 on their microvilli. The fibronectin was detected on presumable collagen fibers and/or fibrin over the exposed smooth muscle layer as well as on fibrin extending between leukocyte aggregation. The spatial microlocalization of integrins was clarified on the leukocytes emigrated in peritonitis, and their ligands were detected on the inflamed peritoneum.

Distribution of Cell Adhesion Molecules (CAM) along the Branching Neurite Surface: Model-Inherited Effects of the Branch Diameters and Mode of CAM Transport

In many cases, an increase in the surface density of cell adhesion molecules (CAM) in the distal parts of a growing neurite is favorable for the neurite elongation. This increase is attained by exocytotic insertion of CAM-containing vesicles into the growth cones with subsequent redistribution of CAM along the cell surface due to lateral diffusion and endocytosis. Using a mathematical model describing these processes, we quantitatively describe conditions providing two qualitatively different profiles in a branching neurite: (i) the CAM surface density increases along both daughter branches, which would be in favor of further outgrowth of both branches, i.e., successful branching, or (ii) the CAM surface density increases along one daughter branch and decreases along another branch, which could lead to the retraction of the latter. The geometric factors and mechanisms underlying the intracellular CAM transport to the daughter growth cones were proved to determine the profile of CAM surface density. A similarity in the diameters of daughter branches, their short lengths, a high value of the lateral transfer constant, and partitioning of CAM transport at the branching point proportionally to the surface areas of daughter branches are in favor of an increase in the CAM surface density along both daughter branches. Asymmetric branching can lead to a decrease in the CAM surface density along the thinner or thicker daughter branch, if CAM trafficking was equally partitioned or was proportional to the branch cross-sectional areas, respectively. The proposed model helps to understand possible relationships between the intracellular CAM trafficking, CAM surface distribution, and geometry of branching of the neurites.

Transendothelial Migration of Monocytes in Rat Aorta: Distribution of F-actin, α-Catenin, LFA-1, and PECAM-1

To determine changes in the distribution of cell adhesion molecules during diapedesis of monocytes in situ, we labeled aortic whole mounts from hypercholesterolemic rats with Texas red-phalloidin and antibodies to LFA-1, PECAM-1, or α-catenin, and analyzed them by laser scanning confocal microscopy. Monocytes transmigrated through circular openings (transmigration passages) formed by pseudopodia that penetrated between adjacent en-dothelial cells. Transmigrating monocytes remained spherical above the endothelium, while spreading beneath it. The transmigration passage was lined by F-actin and partially by α-catenin, suggesting cadherin-mediated heterotypic interactions. LFA-1 was present in clusters at the monocyte cell surface throughout diapedesis, but was concentrated at the margin of the transmigration passage. PECAM-1 was enriched in the endothelial contact regions where the monocytes transmigrated. PECAM-1 was barely detectable in monocytes before and after diapedesis, but appeared during diapedesis at the cell surface in the parts of the monocyte located above the endothelium. PECAM-1 was enriched near the endothelial cell-cell junctions, but was not detected in parts that spread beneath the endothelium. Our results suggest a major role for LFA-1 during diapedesis and reveal dynamic changes in the distribution of PECAM-1, the actin cytoskeleton, and α-catenin during monocyte diapedesis in situ.

Expression of inducible cell adhesion molecules in the normal human lung: immunohistochemical study of their distribution in pulmonary blood vessels

The distribution of cell adhesion molecules in the normal human lung was investigated using antibodies to E-selectin, P-selectin, intercellular adhesion molecule 1(ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Lectin staining by Ulex europaeus type I agglutinin (UEA I) and immunohistochemistry for von Willebrand factor (vWF) was used to visualize a maximum of blood vessels per section. In the bronchial mucosa, staining for P-selectin was positive in ca 90%, and staining for E-selectin, VCAM-1, and ICAM-1 was positive in 40-70% of the vessels stained with UEA I. In the pulmonary circulation (vasa publica) ca 90% of non-capillary vessels stained by anti-vWF expressed P-selectin, 54% VCAM-1, 41% E-selectin, and only ca 20% ICAM 1. The alveolar capillaries were stained consistently by UEA I, but not by the panel of antibodies tested. The alveolar epithelium and, inconstantly, basal cells of the bronchial epithelium were positive for ICAM-1. The distribution pattern of inducible adhesion molecules in normal human lung tissue suggests that a permanent low-grade endothelial activation may exist in particular in the mucosa of the airways, which could be due to the normal antigen exposure via inhaled air.

Immunohistochemical Study of E–cadherin and ZO–1 in Allergic Nasal Epithelium of the Guinea Pig

Nasal epithelial damage during allergic inflammation was studied by observing the distribution of cell adhesion molecule E–cadherin and tight junction (zonula occludens) cell–cell contact associated protein ZO–1. The guinea pig model of nasal allergy, sensitized with intraperitoneally administered ovalbumin (OA) and subsequently challenged with OA intranasally, was used. In control epithelium, E–cadherin immunoreactivity was detected continuously along neighboring epithelial cell borders. ZO–1 spot–like immunoreactivity was detected in the apicolateral portion of epithelial cells corresponding to the tight junction (TJ) position, but no changes in immunoreactivity were found between control and challenged epithelia. In the challenged epithelium of sensitized animals, marked infiltration of eosinophils and structural changes, such as widening of the intercellular spaces and detachment of adjacent epithelial cells, were observed concurrently. In addition, spots negative for E–cadherin immunoreactivity were noted in the epithelium, associated with the extracellular deposition of eosinophil granule proteins. Immunoelectron microscopy revealed a decrease or disappearance of E–cadherin immunoreactivity, which took place not only in regions where intercellular spaces were wide and adjacent epithelial cells were detached, but also at the point of contact between infiltrating eosinophils and epithelial cells. Approximately 87% of eosinophils observed in the challenged epithelium were associated with such loss of E–cadherin immunoreactivity. These results suggest that the intimate epithelial cell contact mediated by E–cadherin is loosened as a consequence of eosinophil infiltration, which may trigger the initial step of subsequent epithelial destruction in allergic states.

Geometry-induced inhomogeneity of distribution of cell adhesion molecules along branching processes

There is evidence that inhomogeneity of lateral distribution of cell adhesion molecules (CAM) in the plasma membrane is crucial for cell motility and growth. It is known that the cells move when the cell-substratum adhesiveness is within a certain critical range. We have carried out simulation studies of the factors governing inhomogeneous CAM distribution along uniform and branching cylinder-shaped cell processes on a flat substrate evenly covered with a ligand. Our model included the following mechanisms: intracellular transportation of CAM to an active (growing) part of the cell, installation in the plasma membrane, lateral diffusive redistribution of mobile CAM, formation and dissociation of CAM/ligand complexes, and CAM internalization by endocytosis. Since the rate of growth is two and one order of magnitude slower than the rate of trafficking and lateral diffusion, respectively, we analyzed steady distributions of CAM. We showed that interplay of the mechanisms included in the model may lead to the occurrence of CAM distributions with inhomogeneity, whose range is critical for translocation of an active part of the cell. It was shown that a difference in the diameters of asymmetric sister branches can cause different inhomogeneous distributions of CAM along these branches and thus can define conditions of their growth. Depending on the branching geometry, one or both sister branches may appear within this critical range, and a difference in the diameters may define a difference in the rate of growth and, correspondingly, in the length. This may constitute the basis for self-control of neurite outgrowth.

Cytochalasin D disrupts the restricted localization of N-CAM, but not of L1, at sites of Schwann cell-neurite and Schwann cell-Schwann cell contact in culture.

The neural recognition molecules L1 and N-CAM have been shown to be preferentially localized at sites of Schwann cell-to-neurite and Schwann cell-to-Schwann cell contact in vitro. In the present study, we investigated the mechanisms underlying the restricted expression of these molecules at the Schwann cell surface, focusing on the possible role of actin filaments. Co-cultures consisting of Schwann cells from newborn mice and explants of dorsal root ganglia from chicken embryos were maintained in the absence or presence of cytochalasin D, an agent disrupting actin filaments. Immunoelectron microscopy with mouse-specific antibodies was carried out to quantify the restricted localization of L1 and N-CAM at the Schwann cell surface in contact with neurites. After 2 days of co-culturing in the absence of cytochalasin D, approximately 65% of the cell cell contacts showed a restricted immunoreactivity for L1 and N-CAM. The accumulation of L1 at contact sites was unchanged in cytochalasin D-treated co-cultures, while the agent strongly reduced the restricted localization of N-CAM to 20% of all cell-cell contacts. The disruption of N-CAM accumulation appeared to be rapid and occurred within 5 h of cytochalasin D treatment. These results indicate that the restricted localization of N-CAM, but not of L1, is sensitive to cytochalasin D treatment, suggesting a dependence on the integrity of the actin network. Thus, different mechanisms may regulate the subcellular distribution of cell adhesion molecules in Schwann cells.

Distribution of cell adhesion molecules in infants with intestinal epithelial dysplasia (tufting enteropathy)

BACKGROUND & AIMS: Intestinal epithelial dysplasia, or tufting enteropathy, is a newly described clinicopathologic entity with refractory diarrhea in infants. Histological abnormalities include villous atrophy, disorganization of the surface epithelium, and basement membrane abnormalities. The aim of this study was to examine defects in intestinal epithelial cell adhesion, differentiation, or proliferation in the pathogenesis of epithelial dysplasia. METHODS: Histological, immunohistochemical, and ultrastructural characteristics of epithelial dysplasia in a group of 6 children were compared with those groups with normal small bowel and other villous atrophy (celiac sprue and microvillous inclusion disease). Distribution of adhesion molecules, markers of cell polarization and proliferation, and the phenotype of intraepithelial lymphocytes were determined. RESULTS: Alterations suggestive of abnormal cell-cell and cell-matrix interactions were present in patients with epithelial dysplasia. They included abnormal distribution of alpha 2 beta 1 integrin along the crypt-villus axis, increased immunohistochemical expression of desmoglein, and ultrastructural changes of desmosomes increased in length and number. No evidence for abnormalities in epithelial cell polarization, proliferation, or T-cell activation was found. CONCLUSIONS: This study strongly suggests a role played by alterations of cell-cell and cell-matrix interactions in the pathogenesis of epithelial dysplasia. (Gastroenterology 1997 Sep;113(3):833-43)

Chronotopic fiber reordering and the distribution of cell adhesion and extracellular matrix molecules in the optic pathway of fetal ferrets

We have examined the age-related reordering of optic axons as they pass through the chiasmatic region in fetal ferrets. Proportions of young and old optic axons were determined from electron micrographs taken sequentially through the prechiasmatic nerve, chiasm, and tract. This "chronotopic" reordering of axons was shown to emerge gradually, beginning rostral to the fusion of the two optic nerves, but continuing to develop caudal to the chiasmatic midline. Segregation of young from old optic axons was most pronounced within the optic tract. We then compared the emergence of this fiber reorganization to the distribution of cell adhesion and extracellular matrix molecules and to the glial architecture within the pathway. Using immunohistochemistry, the distributions of the cell adhesion molecules L1, NCAM, and TAG-1 and the extracellular matrix molecules laminin-1 and chondroitin sulfate proteoglycans (CSPGs) were determined. Among these, only the distribution of CSPGs was observed to change in a manner that complemented the segregation of young from old optic axons. CSPGs were densest in the deeper parts of the optic tract, coincident with radial glial fibers that turn to course within the region of the oldest optic axons. Both the glial architecture and the CSPG distribution form as a consequence of the invasion of the first optic axons, shown by the developmental sequence of each, and by the fact that these glial and molecular features fail to form in the absence of optic axons. The data suggest a model in which the gradient of CSPGs across the depth of the tract contributes to the formation of the chronotopic fiber reordering by providing a relatively unfavorable environment for subsequent axonal growth. The CSPGs may do so by interfering with adhesion molecules on optic axons that normally promote elongation.

Changing patterns of cell adhesion molecules during mouse pelage hair follicle development. 2. Follicle morphogenesis in the hair mutants, Tabby and downy.

Wild-type mice have three main types of hair in their pelage: tylotrichs, awls and zigzags. Tabby mice have a yellowish coat consisting of awls only, whereas downy mice have a sparse grayish coat consisting of unusually fine hairs. The spatial and temporal distribution of cell adhesion molecules (CAMs) during hair follicle morphogenesis was investigated in the mutants and compared with that in nonmutant mice. In Tabby embryos, awl follicles developed normally and showed normal immunostaining patterns for E-cadherin, P-cadherin and N-CAM. Prior to follicle initiation, however, some deviations from normal skin morphology and staining patterns indicated a delay in the development of the basal epidermal layer. On the other hand, the stratum corneum was formed prematurely. Therefore, the lack of tylotrich and zigzag follicles in Tabby mice might be explained by a general defect in epidermal development rather than by abnormal CAM expression. In downy embryos, tylotrich and awl follicles were initiated within the normal time periods, but elongation and differentiation of most follicles were abnormal. At birth, most follicles were small and/or severely deformed but showed normal CAM expression patterns. Extreme distortion and disorientation of follicles seemed to be associated with disintegration of the dermal papilla and abnormal mesenchymal cell condensations between the follicles. This suggests that abnormal hair development in downy mice might result from a defect in dermal rather than epidermal components of the skin.

Distribution of cell adhesion molecules in cultured endothelial cells from human aorta

Distribution of cell adhesion molecules in cultured endothelial cells from human aorta

Spatial synaptic integration in Purkinje cell dendrites

Synaptic integration occurs within a framework of synaptic connections, and cell type-specific, intrinsic and transmitter-gated ion channels. These components are differentially distributed over the somato-dendritic membrane. Recent results from Purkinje cells and pyramidal cells exemplify some of these mechanisms of spatial synaptic integration. This paper focusses on the cerebellar Purkinje cell. In these neurons, the amplitude and distribution of single climbing fibre and parallel fibre EPSP-evoked Ca2+ influx were regulated by the transient outward, IA-like current in the distal (spiny) dendrites. The synaptically evoked Ca2+ influx was graded from a local response involving only a few terminal spiny dendrites to a propagated Ca2+ spike. The climbing fibre-evoked Ca2+ influx in the spiny dendrites was finely graded by parallel fibre-induced depolarization. Climbing fibre and parallel fibre-evoked Ca2+ influx elicited a short lasting afterhyperpolarization that affected subsequent dendritic Ca2+ influx. In addition, inhibitory synaptic input controlled dendritic Ca2+ influx. Interaction between information from different sources along the dendrites is thus controlled by intrinsic potassium conductances and IPSPs. Different electrophysiological properties are found in the cerebellar neurons. Thus, Golgi cells, stellate cells and granule cells seem to integrate on a shorter intrinsic timescale than do Purkinje cells, the output neuron of the cerebellar cortex. The specific mechanisms by which different types of presynaptic neurons specifically innervate a given dendritic compartment remain to be elucidated, but recent results provide some experimental evidence of a differential distribution of cell adhesion molecules between the axonal and the somato-dendritic membrane, suggesting one mechanism contributing to the ordered distribution of synapses during synaptogenesis.

Cell adhesion molecules in inflammation and immunity: relevance to periodontal diseases.

Inflammatory and immune responses involve close contact between different populations of cells. These adhesive interactions mediate migration of cells to sites of inflammation and the effector functions of cells within the lesions. Recently, there has been significant progress in understanding the molecular basis of these intercellular contacts. Blocking interactions between cell adhesion molecules and their ligands has successfully suppressed inflammatory reactions in a variety of animal models in vivo. The role of the host response in periodontal disease is receiving renewed attention, but little is known of the function of cell adhesion molecules in these diseases. In this review we summarize the structure, distribution, and function of cell adhesion molecules involved in inflammatory/immune responses. The current knowledge of the distribution of cell adhesion molecules is described and the potential for modulation of cell adhesion molecule function is discussed.

Distribution of cell adhesion molecules in skeletal muscle from patients with systemic lupus erythematosus.

To investigate the pathophysiology of perivascular mononuclear cell infiltrates observed in skeletal muscle from patients with systemic lupus erythematosus (SLE). Immunocytochemical techniques were used to examine frozen 5 microns sections from the quadriceps needle muscle biopsy specimens of 14 patients with SLE (including seven with infiltrates) for the expression of the cytokine inducible adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Vessels in 6/7 SLE biopsy specimens with perivascular infiltrates expressed VCAM-1 at a density of > 2 vessels/mm2 in contrast with 0/7 SLE biopsy specimens without infiltrates and 1/6 control specimens. In contrast, E-selectin expression was increased ( > 0.3 positive vessels/mm2) in SLE biopsy specimens compared with control tissue regardless of the presence of perivascular infiltration. VCAM-1 and ICAM-1 were also noted on extravascular cells in the infiltrates, being particularly prominent on the intermuscle fibre dendritic processes of CD68+ HLA-DR+ cells. Expression of these cytokine inducible adhesion molecules may be important in the migration of mononuclear cells into skeletal muscle and may be involved in intercellular interactions within the tissue.

Distribution of cell adhesion molecules on CD56++, CD3-, CD16- large granular lymphocytes and endothelial cells in first-trimester human decidua.

Human decidua exhibits a unique infiltrate of large granular lymphocytes (LGL) with a natural killer (NK) cell phenotype (CD56++, CD16-, CD3-). The mechanisms underlying the binding of circulating LGL to vascular endothelium in the decidua and their migration into the decidual stroma were investigated immunohistochemically in first-trimester decidua with antibodies against endothelial adhesion molecules and their counter-receptors on leukocytes. Decidual and peripheral blood LGL were also investigated by flow cytometry. In the immunohistochemical investigations, moderate to large numbers of lymphoid cells in the decidua were found to express the alpha 4 and alpha L integrin subunits, platelet endothelial cell adhesion molecule (PECAM) and intercellular adhesion molecule-1 (ICAM-1). PECAM and ICAM-1 were found on the endothelium of large numbers of decidual blood vessels of all types. Vascular cell adhesion molecule (VCAM), however, was found on the endothelium of only small to moderate numbers of arterioles and venules and a few capillaries, the latter being the main site of migration of leukocytes into the stroma. Weak staining for endothelial leukocyte adhesion molecule (ELAM) was seen only in a moderate number of blood vessels. Flow cytometry revealed expression of the alpha L integrin subunit by 72 +/- 10% and 97 +/- 3% of decidual and peripheral blood CD56+ LGL, respectively, of the alpha 4 integrin subunit by 85 +/- 7% and 90 +/- 5%, of PECAM by 40 +/- 12% and 30 +/- 15%, and of ICAM-1 by 22 +/- 10% and 1 +/- 1%.(ABSTRACT TRUNCATED AT 250 WORDS)

The immunopathology of upper gastrointestinal acute graft-versus-host disease. Lymphoid cells and endothelial adhesion molecules.

Acute graft-versus-host disease is a common complication of allogeneic bone marrow transplantation, but the mechanisms resulting in tissue injury are uncertain. In order to probe the effector phase of upper gastrointestinal acute GVHD, we performed immunopathologic studies of duodenal biopsies obtained from patients with or without GVHD. We evaluated the infiltrating mononuclear cells in both epithelium and lamina propria for expression of CD2, CD4, CD8, CD25, T alpha/beta and gamma/delta receptors, CD16, CD56, CD57 and also studied the distribution of cell adhesion molecules (ELAM-1, VCAM-1, ICAM-1, PECAM-1). In the epithelium, only a minimal T cell infiltrate was observed. In the lamina propria, GVHD tissue (vs. control) had an infiltrate of CD2+ (17.7 +/- 2.9% vs. 7.2 +/- 1.8%; P < 0.04), CD8+ (15.5 +/- 4.4% vs. 4.8 +/- 1.9%, P < 0.04) T lymphocytes. GVHD-positive and control tissues contained similar numbers of CD4+ T cells and natural killer cells (CD56+ or CD57+). ICAM-1 staining of endothelial cells was prominent in GVHD tissues (13.5 +/- 1.1 capillaries/field) and was significantly increased over non-GVHD specimens (7.5 +/- 1.8; P < 0.02). ELAM-1, VCAM-1, and PECAM-1 were similarly distributed in both biopsy groups. These data suggest that effectors of upper GI GVHD include CD2+, CD8+, T lymphocytes infiltrating the lamina propria. Inflammatory cell activation and resultant secretion of cytokines might directly damage the mucosa, but may also upregulate ICAM-1 on local endothelium leading to perpetuation of inflammation by recruitment of additional cytotoxic lymphocytes.

Adhesion receptors of intimal and subintimal cells of the normal synovial membrane.

The distribution of cell adhesion molecules (CAMs) and matrix proteins in the normal synovium of four subjects was studied by immunohistology in order to determine the factors governing the cellular and tissue organization of the intimal and subintimal compartments. Basement membrane proteins, laminin, and collagen type IV, as well as vitronectin and fibronectin, were identified in the intima and there was corresponding expression of integrin and non-integrin receptors (e.g., CD29, CD49b, CD49d, CD49e, CD49f, CD51, CD61, CD44) for these matrix proteins. There were notable differences in CAM expression between intimal, subintimal, and vascular compartments of the synovial membrane. Phenotypic heterogeneity for CAMs involved in cell-cell interactions, particularly CD11a, CD11b, ICAM-1, and HLA-DR, was also present. The range of CAMs expressed by synovial and endothelial cells not only indicates a structural role for these antigens, but also suggests that they may control leucocyte traffic into the membrane, including recruitment of cells into the synovial lining.

Cellular receptors for matrix proteins in normal human kidney and human mesangial cells

In the present study we evaluated the distribution of cell adhesion molecules, referred as very late antigens (VLA), in the normal human kidney and in mesangial cells in culture (MC). In addition, we assessed the functional properties of VLA proteins on MC. Normal human kidney and MC were stained by immunoperoxidase with mouse monoclonal antibodies to VLA proteins. We demonstrated that VLA-3, a protein that binds FN, laminin and collagen, is the predominant VLA protein in the human glomerulus and on MC. VLA-3 is located in the mesangium and on the glomerular visceral epithelial cell and endothelial cell surfaces in contact with the glomerular basement membrane. VLA-1 was demonstrated in the glomerular mesangium and VLA-5, an FN specific receptor, was present in the mesangium on glomerular endothelial cells and on MC. VLA-2 and VLA-4 were not present in the normal glomerulus nor on MC. In functional studies we evaluated the binding of MC to FN coated surfaces and the binding and phagocytosis of FN coated fluorescent beads by MC. We showed that MC bind to FN coated surfaces and that the binding is inhibited by anti-FN antibodies, EDTA and peptides containing the amino acid sequence Arg-Gly-Asp (RGD). In addition, anti-VLA-5 but not anti-VLA-3 antibodies inhibited significantly the binding of MC to FN, MC demonstrated binding and phagocytosis of FN coated beads and, purified FN inhibited both phenomena. By affinity chromatography and immunoprecipitation we demonstrated that MC FN binding proteins and MC VLA proteins are composed of two distinct protein chains that have Mr characteristics similar to those of normal human fibroblasts VLA proteins. In conclusion, the glomerular distribution of VLA-3 suggests that this protein is primarily involved on the adhesion of glomerular cells to basement membranes and matrix. MC FN receptors (VLA-5) mediate the binding of MC to FN and could mediate the phagocytosis of FN coated antigen or immune complexes by mesangial cells.