Activation of endothelial cell phospholipase d by polycations.
V., Suryanarayana, Scribner, W. M. and Natarajan. V.
Department of Medicine, Indiana University School of Medicine,
Indianapolis, IN USA
APStracts 3:0234L, 1996.
Naturally occurring polycations and cationic proteins are implicated
in vascular disorders. It is known that activated leukocytes and
platelets release polycations such as polylysine of varying molecular
sizes into the vasculature and some of these have been described to
be bactericidal. Polycations interact with endothelial cells (ECs)
and cause alterations in permeability and cellular functions. Precise
mechanism (s) by which polycations bring about cellular changes are
unknown. Here we report that the polycations, polylysine (PLys) and
polyarginine (PArg) induce phospholipase D (PLD) activation in ECs.
Polycation-mediated PLD activation was both time- and concentration
dependent and activation of PLD was not due to cytotoxicity. PArg was
more potent as compared to PLys of the same molecular weight in
stimulation of PLD. Treatment with bisindolylmaleimide, a specific
protein kinase C (PKC) inhibitor and heparin attenuated polycation
mediated PLD activation. Furthermore, down regulation of PKC by TPA
(100nM, 18 hours) also blocked polycation-mediated PLD stimulation.
These data suggest that polycation-mediated PLD stimulation probably
involves PKC and may represent an important cellular response to
leukocyte / platelet activation in the vascular endothelium.
Received 13 May 1996; accepted in final form 8 November 1996.
APS Manuscript Number L140-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996