Endotoxin-induced pulmonary leukostasis in the rat: role of platelet-activating factor and tumor necrosis factor.

Abstract

Injection of bacterial lipopolysaccharide (LPS) into experimental animals induces septic shock associated with the release of tumor necrosis factor (TNF) and platelet-activating factor (PAF). Because both TNF and PAF stimulate neutrophil adhesion to endothelial cells in vitro, and because neutrophils are important effector cells in sepsis-induced lung vascular injury, the role of TNF and PAF in LPS-induced lung neutrophil sequestration was investigated. Lung myeloperoxidase (MPO) activity was measured as a quantitative assessment of pulmonary leukostasis. Injection of Salmonella enteritidis LPS into rats caused dose-dependent increases in lung MPO that peaked at 2 hours and persisted for up to 24 hours. Injection of purified human recombinant TNF (2 to 200 micrograms/kg i.v.) mimicked the effect of LPS on lung MPO activity. Injection of synthetic PAF increased lung MPO only at the highest and lethal dose (10 micrograms/kg). Lower doses (0.1 and 1 microgram/kg) of PAF had no effect on lung MPO by itself and did not enhance LPS- or TNF-induced lung neutrophil sequestration. Furthermore, pretreatment of the rats with two different PAF receptor-antagonists, WEB 2086 (10 mg/kg IP) and SRI 63-441 (10 mg/kg IP), failed to block LPS-induced (1 mg/kg) increase in lung MPO. These data suggest that TNF, not PAF, mediates LPS-induced pulmonary neutrophil sequestration in the intact rat.

• Authors: S W Chang
• Journal: The Journal of laboratory and clinical medicine (J Lab Clin Med) Vol. 123 Issue 1 Pg. 65-72 (Jan 1994) ISSN: 0022-2143 [Print] United States
• PMID: 8288963 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Azepines
• Endotoxins
• Lipopolysaccharides
• Platelet Activating Factor
• Quinolinium Compounds
• Triazoles
• Tumor Necrosis Factor-alpha
• SRI 63-441
• WEB 2086
• Peroxidase

Topics

• Animals
• Azepines (pharmacology)
• Endotoxins (pharmacology)
• Lipopolysaccharides (pharmacology)
• Lung (drug effects, enzymology, pathology)
• Male
• Neutrophils (pathology)
• Peroxidase (metabolism)
• Platelet Activating Factor (antagonists & inhibitors, pharmacology)
• Quinolinium Compounds (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Triazoles (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)