DEL1 antibody

Background of DEL1 antibody

Leukocyte recruitment and extravasation to the site of infection or inflammation involves interaction of several adhesion molecules and other molecules promoting leukocyte-endothelial interactions. The vertebrate immune system has an important self check mechanism that prevents it from destroying the host own immune system and regulatory T cells are part of this regulatory suppressive control by interacting with CD80 and CD86 (1). Some modulatory factors on Tregs are Fox3-, CD4, CTLA4, CD28 that promote leukocyte-endotheliall cell interactions have been identified and characterized but only Developmental endothelial Locus 1 (Del-1) is the only functionally important inhibitor of leukocyte adhesion is known so far (2). Leukocyte recruitment to infection/inflammatory site is a well coordinated cascade od adhesive events, including selctin-mediated rolling, firm adhesion of leukocyte of endothelial cells and subsequent trans-endothelial migration. The Del-1 is synthesized and secreted by endothelial cells, this protein can associate with endothelial cell surface and extracellular matrix (3). The Del-1 is regulated during hypoxia and vascular injury and is involved in vascular remodeling and angiogenesis (4). Endothelial cell adhesion to immobilized Del-1 suggest that Del-1 is a ligand for LFA-1 integrin (3). It is shown that soluble Del-1 inhibit the interaction of LFA1 with its major ligand ICAM-1in a Mn+2induced binding of ICAM-1-Fc to murine leukocytes in solution. In vivo, soluble Del-1-expressed as Fc fusion protein when injected 30 minutes prior to thioglycolate induced peritonitis significantly reduced neutorphil accumulation (3). LPS and TNF alfa can significantly reduced the expression of Del-1. The LFA-dependent leukocyte recruitment is an important mechanism, Del-12 may provide a therapeutic target to modulate leukocyte-endothelial interaction diseases.
Cerebral over expression of Del-1 by stereotaxic injection of viral vector ca modulate cerebral angiogenesis and Del-1 may provide a novel and potent means for stimulating cerebral angiogenesis (5). The role of Del-1 in wound healing is not clear but Del-1 expression is significantly increased in the basal keratinocytes and its expression was observed in the root of the hair follicle during normal hair anagenesis suggesting that its stimulatory hair growth effects (6). Del-1 is an extracellular Matrix (ECM) protein produced by endothelial cells in embryos, and it contains three epidermal growth factor repeats (E1-E3) at its N-terminus and two discoidin domains (C1 and C2) at its C-terminus. These function motifs on Del-1 interact with ECM on the endothelial cells. Del-1 mRNA is expressed in brain and lung but it is not expressed in liver, spleen and whole blood though it is present in lung blood vessels. Del-1 is a 480 amino acid protein (MW approximately 58kDa).