Studies on the Pathogenesis of Acute Inflammation

Abstract

The mechanism responsible for the sticking of white blood cells to blood vessel walls in early inflammation continues to pose a challenging problem since this reaction represents the key to an overall understanding of the exudatire events set off by injury.In studies reported earlier, interference with the clotting of blood in vivo failed to prevent the vigorous sticking of leucocytes to vascular endothelium within rabbit ear chambers damaged by heat. As a specific example, maximal activation of the endogenous fibrinolytic system of rabbits by streptokinase (SK) administration did not diminish adherence of circulating white blood cells to endothelium. Since lysis of fibrin in vitro was brisk, failure to modify the sticking reaction could be explained only by assuming that destruction of fibrin on the surfaces of both white cells and endothelium failed to keep pace with newly formed material. In a more direct approach to the problem, the behavior of white cells in damaged chambers was followed after removal of all chemically detectable fibrinogen from the systemic circulation. Even under these conditions, when fibrinogen levels were too low to measure, brisk leucocytic sticking still developed after ear chambers had been damaged by heat (1). From these data it was concluded that the sticking reaction was not causally related to formation of fibrin.Such consistent failure to halt white cell sticking led to an investigation of specific pharmacological substances known to block the clotting of blood in vivo. From preliminary observations previously reported, it was anticipated that one such agent, heparin, would materially impede the reaction (2). Although many anticoagulants were available, heparin and warfarin sodium were selected because of extensive use by others; both were of low toxicity in the ranges used; and because each could be administered parenterally to insure adequate blood levels. Furthermore, both agents were known to prevent not only the local but also the generalized Shwartzman reac-*