Paf mediates neutrophil adhesion to thrombin or tnf-a- stimulated endothelial cells under physiologic shear stress.. Macconi, Daniela, Marco Foppolo, Simona Paris, Marina Noris, Sistiana Aiello, Giuseppe Remuzzi, and Andrea Remuzzi. Mario Negri Institute for Pharmacological Research, Via Gavazzeni, 11, 24125 Bergamo, Italy, Division of Nephrology and Dialysis, Ospedali Riuniti di Bergamo, Largo Barozzi, 1, 24128 Bergamo, Italy
APStracts 2:0077C, 1995.
Platelet activating factor (PAF) is known to modulate polymorphonuclear leukocyte (PMN) adhesion to endothelial cells cultured under static conditions and activated by thrombin. By contrast, there are no data on the role of PAF in PMN adhesion to cells exposed to flow conditions and activated by stimuli other than thrombin. Here we used the PAF receptor antagonist L -659,989 to evaluate PMN adhesion to human umbilical vein endothelial cells (HUVEC) in basal conditions or upon challenge with thrombin or tumor necrosis factor (TNF) [alpha]. Experiments were performed under dynamic flow using a parallel plate flow-chamber and a computer based image analysis system. Rolling and adhesion of PMNs to endothelial cells significantly increased upon stimulation with thrombin. Thrombin-stimulated HUVEC also synthesized higher amounts of PAF than untreated cells. Pretreatment of PMNs with L -659,989 significantly reduced their rolling and adhesion to thrombin -activated HUVEC. Stimulation of HUVEC with TNF-[alpha] significantly increased the number of rolling and adherent PMNs as compared to untreated cells. Adhesion of PMNs to and migration across TNF-a-stimulated HUVEC were reduced by L -659,989, while cell rolling was unchanged. We conclude that PAF mediates leukocyte interaction under flow conditions with HUVEC activated by inflammatory stimuli. 

Received 14 November 1994; accepted in final form 18 January 1995.
APS Manuscript Number C668-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 February 1995.