Human Vascular Permeability Factor

Human vascular permeability factor (hVPF) is a glycoprotein that promotes fluid and protein leakage from blood vessels.The function of hVPF is at present unknown, but the potent bioactivities of this protein suggest that it could act during inflammation, wound healing, and tumor angiogenesis.hVPF was purified from serum-free conditioned medium of the human histiocytic lymphoma cell line U937 as a disulfide-linked dimeric 40-kDa protein that promoted dermal blood vessel leakage in guinea pigs at a dose of 20 ng (3 x lo-' M) and promoted in vitro endothelial cell growth at concentrations as low as 50 pM.Multiple forms of hVPF with apparent PI values > 7.5 were resolved using pH gradient electrophoresis.Antibodies against guinea pig vascular permeability factor were found to cross-react with hVPF.The N-terminal amino acid sequence of hVPF was similar to, but not identical with, the N-terminal sequence of guinea pig vascular permeability factor.A protein known as vascular permeability factor (VPF)' was first identified as a secreted product of guinea pig line 10 tumor cells in vitro (Senger et al., 1983) and has since been found to be synthesized by numerous human and rodent tumor cell lines (Senger et al., 1986).VPF is an extremely potent agent in promoting fluid and protein extravasation.It has been hypothesized (Dvorak et al., 1981) that the leakiness that is sometimes associated with tumor vasculature (Brown et al., 1988;Gerlowski and Jain, 1986;O'Connor and Bale, 1984;Song and Levitt, 1971) may be explained, at least in part, by the production of VPF by tumors.This hypothesis is supported by experiments in which antibodies against VPF were shown to inhibit the accumulation of ascites fluid in tumor-bearing animals (Senger et al., 1983).gVPF is a -40-kDa protein consisting of disulfide-linked subunits of -18-24 kDa.A single N-terminal amino acid sequence was obtained for intact gVPF and for the individual