Disease relevance of PECAM1

• EndoCAM (CD31) was constitutively expressed in all types of endothelial cells, sinus macrophages, and in epithelioid granulomas [1].
• Functional implication of the hydrolysis of platelet endothelial cell adhesion molecule 1 (CD31) by gingipains of Porphyromonas gingivalis for the pathology of periodontal disease [2].
• Expression of von Willebrand's factor, CD34, CD31, and vascular endothelial growth factor in uterine leiomyomas [3].
• Brain metastatic lesions of the selected variants contained significantly more CD31-positive blood vessels than metastases of the non-selected cell line [4].
• The average microvessel density determined for MVC (microvessel count) using CD31 was 60.64 for hemangiomas and 59.64 for pyogenic granulomas, while angiogenic index determined using vWF was 64.24 and 62.20 in these lesions [5].

High impact information on PECAM1

• The binding of anti-CD31 monoclonal antibodies as measured by fluorescence-activated cell sorting correlated with the CD31 types of homozygous cell lines [6].
• The immunoreactivity of CD31 phenotypes with anti-CD31 monoclonal antibodies was compared by flow cytometry [6].
• To assess the relevance of CD31 matching to bone marrow transplantation, we performed CD31 typing of 46 recipients of bone marrow (32 without GVHD and 14 with severe [grade III or IV] acute GVHD) and their HLA-identical sibling donors [6].
• Among the transplant recipients, 71 percent of those with acute GVHD had CD31 genotypes that were not identical to the donor's genotype, as compared with 22 percent of the recipients without GVHD (P = 0.004) [6].
• Polymorphism of adhesion molecule CD31 and its role in acute graft-versus-host disease [6].

Chemical compound and disease context of PECAM1

• Increasing evidence has implicated PECAM-1 in a plethora of biological phenomena, including modulation of integrin-mediated cell adhesion, transendothelial migration, angiogenesis, apoptosis, cell migration, negative regulation of immune cell signalling, autoimmunity, macrophage phagocytosis, IgE-mediated anaphylaxis and thrombosis [7].
• In a comparative analysis, CD31 was not expressed by any of the melanoma cell lines, whereas TIE-1 (tyrosine kinase with Ig and epidermal growth factor homology domains-1) was strongly expressed in the highly aggressive tumor cells with a low level of expression in one of the poorly aggressive cell lines [8].
• Expression of CD31 in resveratrol-treated gliomas was followed immunohistochemically to study the effect of resveratrol on the glioma-induced angiogenesis [9].
• Chemotactic properties of ICAM-1 and PECAM-1 on neutrophil granulocytes in ulcerative colitis: effects of prednisolone and mesalazine [10].
• METHODS: Ten colonic lymphangiomas, diagnosed and resected endoscopically between 1992 and 1999, were microscopically examined and immunohistochemically stained with CD31, CD34, Factor VIII-related antigen, and smooth muscle actin [11].

Biological context of PECAM1

• To determine if the PECAM1 locus colocalizes with any of the loci for these adhesion molecules, PCR-based analysis of a regional mapping panel for human chromosome 17 was conducted [12].
• We found that the PECAM1 locus is on the long arm of chromosome 17, in the region q23-qter [12].
• CD9 and PECAM-1 thus appear to have an intracellular distribution identical to GPIIb-IIIa, a major aggregation platelet receptor [13].
• We determined the role of the heterophilic interaction of alphavbeta3 integrin on endothelial cells with CD31 on leukocytes in mediating leukocyte-endothelial cell interactions [14].
• DC101 therapy resulted in a 50% decrease in overall VEGFR-2 phosphorylation and a 15-fold and 8-fold increase in endothelial cell (CD31-positive) and tumor cell apoptosis, respectively [15].

Anatomical context of PECAM1

• On normal resting platelets, immunolabeling for CD9 and PECAM1 was found lining the plasma membrane and the luminal face of the open canalicular system [13].
• Analysis of a somatic cell hybrid chromosome panel established that the PECAM1 gene is on chromosome 17 [12].
• The confluency-dependent inhibition of expression of E-selectin was at least partly mediated through the cell junctional protein, platelet/endothelial cell adhesion molecule-1 (PECAM-1) [16].
• However, anti-alphavbeta3 integrin MoAb had no significant inhibitory effect on the eosinophil adhesion to IL-4-stimulated or unstimulated HUVECs without CD31 stimulation of HUVECs [14].
• The capillaries expressed the endothelial cell markers von Willebrand factor and CD31 antigen [17].

Associations of PECAM1 with chemical compounds

• Even if the studies performed are few, it was found an association between young AMI and polymorphism C-260T in the CD14 gene, between coronarics atherosclerosis and polymorphism A516C in the E Selectin gene or polymorphisms Leu125Val and Ser563Asn in the PECAM1 gene [18].
• Transfected COS-7, mouse 3T3 and L cells expressed a 130-120-kD glycoprotein on their cell surface that reacted with anti-PECAM-1 polyclonal and monoclonal antibodies [19].
• CD31 stimulation of HUVECs increased the adhesive function of alphavbeta3 integrin to its ligand RGD peptide, the binding of which reached a maximum at 10 minutes after the stimulation, and the CD31-induced alphavbeta3 integrin activation on HUVECs was inhibited by inhibitors of protein kinase C and phosphatidylinositol 3 kinase (PI3-kinase) [14].
• In immune precipitate phosphatase assays, there was tyrosine dephosphorylation of PECAM-1 [20].
• Glycogen synthase kinase 3 (GSK-3beta) serine phosphorylation (inactivation) was blunted in PECAM-1-null ECs after histamine treatment or shear stress [21].

Physical interactions of PECAM1

• PECAM-1 was coimmunoprecipitated by anti-SH-PTP2 from EC extracts as a major binding protein, and the level of association increased when PECAM-1 was tyrosine phosphorylated [22].
• Our data show that moesin co-immunoprecipitated with PECAM-1 in lysates from thrombin-stimulated, but not resting platelets [23].
• In conclusion, PECAM-1/CD31 appears to be one of the molecules functionally coupled to PI3K, suggesting that this enzyme may represent a common pathway of integrin and adhesiveness regulation in leukocytes [24].
• Peptido-precipitation analysis revealed that tyrosine-phosphorylated peptides encompassing residues 658-668 and 681-691 of PECAM-1 bound specifically to both protein-tyrosine phosphatases SHP-1 and SHP-2 [25].
• We show that CD38+ B-CLL cells bind to murine fibroblasts transfected with the CD31 ligand [26].

Enzymatic interactions of PECAM1

• PECAM-1 (CD31) functions as a reservoir for and a modulator of tyrosine-phosphorylated beta-catenin [27].
• Rather, PECAM-1 supports homophilic binding on HUVEC with similar characteristics to those we have previously reported for leukocytes and becomes tyrosine phosphorylated after homophilic PECAM-1 and integrin/fibronectin engagement [28].
• PECAM-1 is more highly phosphorylated in endothelial cells overexpressing c-Src, and in in vitro kinase assays, c-Src can phosphorylate a glutathione S-transferase (GST)-PECAM cytoplasmic tail fusion protein [29].
• When endothelial cells are stimulated by fluid shear stress, PECAM-1 is tyrosine phosphorylated and activates the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signalling cascade [30].

Co-localisations of PECAM1

• Furthermore, PECAM-1 co-localized with moesin at the cell periphery and in filopodia of glass-activated platelets [23].

Regulatory relationships of PECAM1

• Furthermore, anti-alphavbeta3 integrin MoAb and RGD peptide as well as soluble CD31 inhibited endothelial CD31-induced enhancement of eosinophil adhesion to IL-4-stimulated HUVECs [14].
• Confocal microscopy demonstrated that adult glomeruli display nestin immunoreactivity in vimentin-expressing cells with the podocyte morphology and not in cells bearing the endothelial marker CD31 [31].
• Also, VEGF/LacCer-induced PECAM-1 expression and angiogenesis was mitigated by protein kinase C and phospholipase A2 inhibitors [32].
• In normal controls, PECAM was intensely expressed and VCAM-1 was weakly expressed [33].
• This was tested by assessing the role(s) of CD38 after signaling with agonistic anti-CD38 monoclonal antibodies or by blocking the interactions taking place between CD38 and CD31, its counterreceptor [34].

Other interactions of PECAM1

• CD9 and PECAM-1 were found lining the membrane of the same granules that contained fibrinogen and vWF in their matrix [13].
• Platelet alpha-granule and plasma membrane share two new components: CD9 and PECAM-1 [13].
• PECAM-1/CD31, another cell-cell junctional adhesive molecule, was tyrosine phosphorylated with similar kinetics in response to VEGF [35].
• Immunostaining showed that the vascular structures expressed CD31, CD34, and CD105 (endoglin), which were not expressed by stromal fibroblastic cells [36].
• A rapid translocation of SH-PTP2 into cell-cell adhesion sites, where PECAM-1 was localized, occurred in mechanically stimulated cells [22].

Analytical, diagnostic and therapeutic context of PECAM1

• We have determined the chromosomal and regional location of the gene encoding PECAM-1 (termed PECAM1 by GBD nomenclature) using a polymerase chain reaction (PCR)-based analysis of somatic cell hybrids [12].
• To confirm this observation and obtain a more precise localization of the PECAM1 locus, fluorescence in situ hybridization was conducted [12].
• Co- culture of subconfluent ECs with PECAM-1- coated beads or with L cells transfected with full-length PECAM-1 or with a cytoplasmic truncation PECAM-1 mutant, inhibited E-selectin expression [16].
• Ligation of CD31 (PECAM-1) on endothelial cells increases adhesive function of alphavbeta3 integrin and enhances beta1 integrin-mediated adhesion of eosinophils to endothelial cells [14].
• PECAM-1 immunohistochemistry showed the BPD group had decreased staining intensity and abnormal distribution of alveolar capillaries [37].

References