Effect of nerve growth factor on endothelial cell biology: proliferation and adherence molecule expression on human dermal microvascular endothelial cells

In addition to its effect on the central nervous system, nerve growth facto r (NGF) appears to play a key role in the initiation and maintenance of inf lammation in many organs. NGF degranulates mast cells, recruits inflammator y cellular infiltrates and activates T cells. Extravascular migration of le ukocytes is initially controlled by the interaction of cell surface adhesio n molecules of leukocytes and endothelial cells. A marked upregulation of N GF in keratinocytes is also observed in conditions characterized by angioge nesis such as psoriasis and wound healing. In this study we investigated th e role of NGF in inflammation by studying its effects on endothelial cell p roliferation and intracellular adhesion molecule expression by endothelial cells. The effect of NGF on human dermal microvascular endothelial cell (HD MEC) proliferation was measured using the hexosaminidase assay. ICAM-1 expr ession on HDMEC was measured by ELISA. The function of ICAM-1 was assessed by adherence of peripheral blood mononuclear cells (PBMC) to HDMEC using Cr -51-labeled PBMC. There was a significant int crease in proliferation of HD MEC stimulated with NGF as compared to unstimulated HDMEC (P < 0.001). NGF neutralizing antibody decreased the mitogenic effect of NGF significantly ( P < 0.05). NGF also increased ICAM expression on HDMEC as compared to unsti mulated HDMEC (P < 0.05). NGF-neutralizing antibody decreased ICAM expressi on on NGF-stimulated HDMEC: (P < 0.05). The percentage of PBMC adherence wa s higher in NGF-stimulated HDMEC (P < 0.001). Anti-ICAM antibody decreased PBMC adherence. In the study reported here, the role of NGF in two importan t aspects of inflammation, i.e. angiogenesis and inflammatory cell recruitm ent at the site of inflammation, was investigated.