Prevention by granulocyte depletion of increased vascular permeability of sheep lung following endotoxemia.

Abstract

A B S T R A C T To see whether circulating granulocytes are necessary for the lung vascular reaction to endotoxin, we measured the endotoxin response in chronically instrumented sheep before and after granulocyte depletion with hydroxyurea. Granulocyte depletion did not affect the pulmonary hypertension caused by endotoxin (peak mean pulmonary artery pressures = 38+2 cm H20 before depletion and 42+2 after depletion, P = NS). The late phase increase in lung lymph flow after endotoxin was significantly lower in the granulocytopenic animals as reflected by lung lymph flow (mean steady state lymph flow before depletion = 30.6+2.0 SE ml/h; mean steady state lymph flow after granulocyte depletion = 15.4+1.0; P < 0.01) even though late phase pulmonary vascular pressures were similar before and after granulocyte depletion. Lung lymph protein clearance (lymph flow x lymph/plasma protein concentration) was also significantly lower after granulocyte depletion (mean steady state before depletion = 21.4 + 1.4 SE ml/h; and after depletion = 10.4+ 1.0; P < 0.01). We conclude that circulating granulocytes are necessary for the development of increased lung vascular permeability to fluid and protein following endotoxin. The pulmonary vasopressor effects of endotoxin in sheep are independent of granulocytes.

C5a and TNF-α Up-Regulate the Expression of Tissue Factor in Intra-Alveolar Neutrophils of Patients with the Acute Respiratory Distress Syndrome

“…Attenuation of neutrophil accumulation in the lungs, by using molecules inhibiting neutrophil adhesion, decreased the severity of lung injury (37). In addition, data from animal studies indicate that neutrophil depletion markedly attenuates the severity of endotoxemia-induced ALI (38,39).…”

Influence of Granulocytes on Brain Edema, Intracranial Pressure, and Cerebrospinal Fluid Concentrations of Lactate and Protein in Experimental Meningitis

“…The most important cells involvedin such inflammation-associated tissue damage are the neutrophils. Granulocytes have been implicated as playing a key role in the development of adult respiratory distress syndrome [32,33], even though recent data suggest that this syndrome can also develop in neutropenic individuals [34]. In other situations granulocytic enzymes may develop their harmful activity in conjunction with microbial enzymes, a mechanism that has been documented in the bronchial system of children with cystic fibrosis colonized with Pseudomonas aeruginosa [35].…”

Effects of Endotoxin Induced Lung Injury and Exercise in Goats/Sheep

“…Thromboxane inhibitors attenuate pulmonary hypertension but not lung permeability changes (12-13). In addition, neutrophil depletion reduces increased pulmonary vascular permeability without affecting pulmonary hypertension (14). Other agents have been shown to attenuate both hypertension and edema including prostaglandin E 2 (15), calcium channel inhibitors (16), and steroids (17)(18).…”