(Circulation. 1996;93:2152-2160.)
© 1996 American Heart Association, Inc.
Articles |
Plasmin Promotes an Endothelium-Dependent Adhesion of Neutrophils
Involvement of Platelet Activating Factor and P-Selectin
From the Dipartimento di Fisiopatologia Clinica (G.M., E.L., A.D., G.E.), Istituto di Nefro-Urologia (G.C., S.R.S.), Università di Torino, Italy; IBMP-Institut fur Biomedizinische und Pharmazeutische (L.S.), Heroldsberg, Germany; Servizio di Medicina Nucleare (G.C., P.G.D.), Ospedale Molinette, Torino, Italy; and Cattedra di Nefrologia, Dipartimento di Scienze Cliniche e Biologiche (G.C.), II Facoltà di Medicina, Università di Pavia, Varese, Italy.
Correspondence to Dr G. Camussi, Cattedra di Nefrologia, Dipartimento di Scienze, Cliniche e Biologiche, Viale Borri 57, 3100 Varese, Italy.
Background The adhesion of leukocytes to the endothelium and the edema of vessel wall may cause vascular reocclusion after thrombolytic therapy. The aim of this study was to evaluate the role of platelet activating factor (PAF) and P-selectin on the adherence of polymorphonuclear neutrophils (PMN) to the endothelium and of PAF on the increased vascular permeability induced by tissue-type plasminogen activator, streptokinase, and plasmin.
Methods and Results We studied (1) the adhesion of 111In-labeled PMN to human umbilical cord vein–derived cultured endothelial cells (HUVEC), (2) the transfer of 125I-labeled albumin across HUVEC monolayers, and (3) the adhesion of PMN to isolated bovine coronary arteries under flow conditions. It was found that the adhesion of PMN, induced by tissue-type plasminogen activator, streptokinase, and plasmin, correlated with the synthesis of PAF by HUVEC and was inhibited by WEB 2170, a PAF receptor antagonist. The adhesion of PMN was also inhibited by the treatment of HUVEC with anti–P-selectin antibodies or of PMN with soluble P-selectin or with anti-CD18 monoclonal antibodies. Plasmin also increased the permeability of HUVEC monolayers, an effect that was partially prevented by WEB 2170. Moreover, plasmin promoted the synthesis of PAF from isolated bovine coronary arteries and the adherence of PMN to the endothelium under flow conditions. The pretreatment of PMN with WEB 2170 or with soluble P-selectin prevented adhesion.
Conclusions The synthesis of PAF by endothelial cells at the site of plasmin generation and the endothelial expression of P-selectin may render the endothelial cell surface proadhesive for neutrophils and may favor a local increase in vascular permeability.
Key Words: leukocytes • platelet-derived factors • endothelium • cells
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