Recombinant Human CD31/PECAM-1 Fc Chimera Protein, CF

CD31, also known as platelet endothelial cell adhesion molecule-1 (PECAM-1), is a 130 kDa heavily glycosylated transmembrane protein belonging to the immunoglobulin (Ig) superfamily of cell adhesion molecules (1, 2). CD31 is highly expressed on endothelial cells and at a lower level on platelets, granulocytes, macrophages, dendritic cells, T and B cells, and natural killer (NK) cells. It is involved in cell adhesion and is required for transepithelial migration of leukocytes (TEM) (3, 4). CD31 is composed of an extracellular domain (ECD) of 574 amino acids (aa) containing six Ig-like domains, a transmembrane domain, and a 118 aa cytoplasmic domain (5). The latter undergoes alternative splicing which generates multiple isoforms showing altered adhesive properties compared to full length CD31 (6). The human CD31 ECD shares 63% and 61% aa sequence identity with mouse and rat CD31, respectively. CD31 acts as a homophilic receptor through its extracellular domain and is involved in downstream signaling via its cytoplasmic domain (7). This domain contains highly conserved ITIM motifs which, once tyrosine phosphorylated, recruit and activate the signaling molecules Src and SHP-2 (1, 8). The resulting inhibition of TCR signaling increases the activation threshold of T cells, thus reinforcing peripheral tolerance and preventing development of autoimmunity (9). CD31 additionally regulates immune responses by acting as a key inhibitory receptor in dendritic cell development (10). Besides its role in TEM, CD31 appears to regulate T cell trafficking through a complex coordination of endothelial cell junctions and T cell extravasation (11). In vitro, a 110 kDa soluble form of CD31 is released following shedding of the extracellular domain during endothelial cell apoptosis (12). This ectodomain has also been identified in the serum of patients suffering from myocardial infarction, acute ischaemic stroke, and multiple sclerosis, conditions that involve tissue damage and endothelial cell apoptosis (13-15).