Enhancement of granulocyte-endothelial cell adherence and granulocyte-induced cytotoxicity by platelet release products.

Abstract

Complement-stimulated granulocytes adhere to and induce significant 51Cr release from endothelial cells in vitro. Platelets were stimulated to undergo release, and these release products significantly enhanced granulocyte-endothelial cell adherence and granulocyte-induced 5tCr release from endothelial cells. Platelet serotonin appeared to mediate these phenomena because serotonin antagonists blocked both the enhanced endothelial adherence and 5tCr release. In addition, added serotonin mimicked the effect seen with the stimulated platelets upon granulocyte-endothelial cell adherence and cytotoxicity completely. This enhancement appeared to be due to serotonin effects upon both the granulocyte and endothelial cells. These data suggest that a released platelet constituent might modulate in vivo granulocyte-endothelial cell interactions in clinical disorders.Endothelial injury, followed by subendothelial cell proliferation, is thought to play a prominent role in virtually all models of vascular injury and atherogenesis (1). Speculation on the etiology ofthe proliferative response has centered upon the role of platelet-derived "growth factors" (2); however, the mechanisms for initiating endothelial cell damage have been given less attention. Recent studies from our laboratory have focused upon the damaging effects on the vascular endothelium of granulocytes (polymorphonuclear leukocytes) that have been stimulated by various immunologic stimuli, particularly activated complement components (3). These studies were fostered by our interest in the acute pulmonary dysfunction that occurs early in hemodialysis (4). Abnormalities in pulmonary dynamics that hemodialyzed patients manifest also may be reproduced in laboratory animals by reinfusing them with autologous plasma that had been allowed to contact hemodialyzer membranes (5, 6); pulmonary microvascular damage and associated pulmonary interstitial edema were evident in these animals (5, 6).By visualizing the microvasculature of rat mesenteries through laser intravital microscopy, Hammerschmidt et al (7) observed that infused complement, particularly C5a, first promoted granulocyte adhesion to endothelium, followed shortly thereafter by plasma leak into interstitial tissues (7). A potential mechanism for this vascular damage was suggested by in vitro studies ofcultured endothelial cells (8). When exposed to granulocytes and a source of activated complement, labeled endothelial cells released chromium, and this release was largely inhibited by superoxide dismutase and catalase. It appeared likely, therefore, that the complement-stimulated production of reactive oxygen species by granulocytes underlies the endothelial cell alteration, a surmise validated by recent studies of others (9) methods (8, 11, 12). Cells were cultured under 95% air/5% CO2 at 370C in medium 199 containing 20% calf serum (GIBCO); they were used =5 days after explanation, just prior to reaching confluence, and were identified as endothelium by their reaction with rabbit antisera to human Fa...

Neutrophil-induced injury of rat pulmonary alveolar epithelial cells.

“…A requirement for close contact between neutrophil and target cell has been described in other systems (35,54,55). We noted that cytotoxicity in our system decreased when adherence of neutrophils to epithelial cells was reduced by pretreatment with anti-Mol antibody (specific for an adhesion-promoting neutrophil glycoprotein [gp155,94] [46]).…”

Platelet‐leukocyte interaction in adhesion to endothelial cells induced by platelet‐activating factor in vitro

“…This result is in agreement with that of Boogaerts et al (1982), who have shown that platelets release products which enhance granulocyte-endothelial cell adherence. Such an augmentation by direct interaction of PMNs with platelets has also been reported to occur in a nylon-fibre assay of PMN adherence (Rasp et al, 1981).…”

Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival.

“…The adherence of granulocytes to vascular endothelium is the initial step in the emigration of these cells into the tissues, and as such is central to the process of inflammation (40). This adherence of granulocytes to endothelium has been shown to be influenced by bacterial products and components ofthe complement cascade (41), platelet products (42), and more recently by rH TNFa (43). These data suggest that while GM-CSF may be of great importance in stimulating human neutrophil and eosinophil function at the site of inflammation, cell-derived products other than GM-CSF are responsible for stimulating granulocyte adherence leading to their emigration into inflammatory sites.…”