Increased interaction of vascular endothelium and leucocytes after administration of antiplatelet serum: role in the developing vascular defect.

Abstract

SUMMARY Antiplatelet serum (APS) induced an increase in the stickiness of white cells which manifests itself in the increase in number of granulocytes rolling along or sticking to the venous endothelium. Lidocaine treatment prevented the increased stickiness of white cells and, at the same time, the microvascular haemorrhage developing after APS. It can be assumed that increased stickiness of white cells after APS may contribute to endothelial damage.Administration of antiplatelet sera (APS) is the most selective method to eliminate platelets from the circulation for the study of thrombocytopenic conditions. Although the specificity of APS was questioned by the early observation that such sera cross-reacted with a vascular endothelial antigen (Bedson, 1922;Elliott and Whipple, 1940), haemorrhagic vascular defects, which developed after the injection of APS, were attributed to severe thrombocytopenia (Kitchens and Weiss, 1975).Administration of APS to rats causes a rapid and prolonged disappearance of circulating platelets. However, little consideration has previously been given to the transient leucocytopenia that also occurs after administration of APS and the possible role of granulocytes in the development of the ensuing microvascular lesions. During experiments on the microcirculation of rats treated with APS, a striking increase in the number of marginating (rolling) leucocytes was observed along the vascular wall immediately after the APS infusion. In the present study it is shown that administration of APS significantly increased the adhesive behaviour of leucocytes to venous endothelium. This transient effect may play a significant role in the vascular endothelial damage of small blood vessels that occurs in rats rendered thrombocytopenic by APS. Material and methodsAntiserum to rat platelets was produced in rabbits.'Present address: Korvin 0. Hospital, 1071-Budapest, Hungary Received for publication 7 June 1978 The serum used in the present study (0-2 ml/rat) regularly produced thrombocytopenia of about 104 platelets per microlitre of blood. The antiserum agglutinated in vitro rat platelets but did not interreact with rat lymphocytes and granulocytes. Venous blood samples were taken from the cut rat tail. Total leucocyte counts were obtained by the haemocytometer method, and differential counts were made on 200 cells from the Giemsa-stained smears taken at the same time. Platelets were counted by phase microscopy (Brecher and Cronkite, 1950). Male rats (Sprague-Dawley, CFY strain, 150-180 g body weight) were anaesthetised with pentobarbital sodium (60 mg/kg subcutaneously supplemented with 5 mg/kg intramuscularly at 30-minute intervals).Mesoappendix microcirculation was prepared according to Zweifach (1965). Microvasculature was observed through a long-distance focusing objective (UM-20, Leitz) and the microscopic field was enlarged electronically (up to x 6000) by a television camera and monitor system. The diameter of the vessels was determined by the calibrated scale of the monitor screen. The mic...