The Role of Granulocytes in Endotoxin-induced Vascular Injury

Abstract

This study examines the role of neutrophils (PMN) in the pathogenesis of the endothelial lesion induced by a single sublethal dose of endotoxin. It is intended to clarify whether the margination of PMN on endothelium after endotoxin causes intimal injury or is a response to it. Neutropenic rabbits had mean PMN counts of 33/cu mm 72 hr after nitrogen mustard (HN2). They were heparinized and given either intravenous endotoxin or saline and were sacrificed 30-60 min later. Preterminal blood samples were positive for the presence of endothelium in 77% of endotoxin-treated neutropenic rabbits, in 87% of endotoxin-treated normal rabbits, and in only 12% of neutropenic rabbits given saline. Sections of aorta revealed marked abnormalities of endothelium in rabbits receiving endotoxin, whether neutropenic (90% had lesions) or normal (85% had lesions). Endothelial abnormalities included vacuolation and lysis, marked subendothelial edema, and desquamation. Similar lesions in control neutropenic rabbits were not found, and mild abnormalities were seen only rarely. These data indicate that neutropenia does not protect rabbits from endothelial injury due to endotoxin. They further suggest that HN2 may cause endothelial damage either directly or secondary to the effects of neutropenia.

The Role of Blood Platelets in the Precipitation of Soluble Fibrin by Endotoxin

“…It was recently shown that infusions of norepinephrine into ancrodinfused rabbits can substitute for endotoxin injection and result in microclot formation (Miiller-Berghaus & Mann 1973). Furthermore, it might be conceivable that endotoxin-induced endothelial damage represents a surface for the precipitation and polymerization of soluble fibrin as Gaynor (1973) previously demonstrated endotoxin to cause endothelial injury. Thus, present and recent experiments (Miiller-Berghaus & Eckhardt 1975) indicate that platelets as well as leucocytes are essential to the activation of intravascular coagulation and formation of circulating soluble fibrin, but are not necessary for the second step in microclot formation, i.e.…”

“…The generation of glornerular microclots is a biphasic event. Firstly, the coagulation system has to be activated to form soluble fibrin monomer complexes (soluble fibrin), and secondly, these complexes have to be precipitated by a process independent of the coagulation mechanism (Muller- Berghaus & Hocke 1972, 1973.…”

Pulmonary Lesions Induced by a Pasteurella Haemolytica Cytotoxin Preparation in Calves

“…A similar train of events although less severe i. e. accumulation, margination, degranulation and fragmentation of leukocytes in the pulmonary microcirculation with secondary alveolar flooding or alveolar collaps, is seen after systemic endotoxin administration in sheep (27) and rhesus monkeys (30). Endothelial lesions probably precede the intravascular leukocytic accumulation and degeneration as endotoxin induced endothelial lesions in neutropenic animals (14,31) and caused endothelial cell injury in witro (18). Alveolar flooding has also been observed after systemic endotoxin administration in calves (29,37).…”

Activation of Intravascular Coagulation by Endotoxin: the Significance of Granulocytes and Platelets

“…(Muller-Berghaus & Eckhardt, 1975). Corresponding figures were published by Forman et al(1969) and Gaynor (1973). Most interestingly microclot formation occurred in some animals with platelet counts below 5 x 1o9/I., one of these animals exhibiting only 0.5 x 10~11.…”