Control of local blood flow in pulmonary inflammation: role for neutrophils, PAF, and thromboxane.
The intrapulmonary instillation of C5a results in a local inflammatory response that, in this site, is accompanied by a decrease in local blood flow. Reversal of this decrease by vasodilators or the thromboxane synthesis inhibitor dazmegral has been shown to result in enhanced lung inflammation. In the present study the mechanisms underlying the decrease in flow in pulmonary inflammation were investigated in the rabbit in vivo and in the isolated blood-perfused rabbit lung. In vivo, the decrease in local blood flow was shown to be dependent on circulating neutrophils. In the isolated blood-perfused lung, inflammation induced by airway instillation of C5a was similar histologically to that seen in vivo and was also accompanied by a decrease in local blood flow. The decrease in blood flow appeared to require circulating neutrophils and was prevented by dazmegral and the platelet-activating factor (PAF) antagonists WEB 2086 and L-659,989. Furthermore, no decrease occurred in aspirin-treated lungs perfused with normal blood, suggesting that the source of thromboxane was lung rather than circulating cells. The decrease in blood flow in inflammation did not appear to be a consequence of hypoxic vasoconstriction. Inflammation in the guinea pig lung was also accompanied by a decrease in local blood flow and was also prevented by dazmegral and PAF antagonists. We conclude that local inflammation in the lung is accompanied by a decrease in blood flow that involves neutrophils and the lipid mediators PAF and thromboxane. We suggest that this form of negative feedback by the neutrophil serves to control the inflammatory response.
Hellewell
P G
PG
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver 80206.
Henson
P M
PM
Downey
G P
GP
Worthen
G S
GS
D000818:Animals; D015936:Complement C5a / Q000494:pharmacology; D005246:Feedback; D005260:Female; D006168:Guinea Pigs; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009504:Neutrophils / Q000502:physiology; D010972:Platelet Activating Factor / Q000502:physiology; D011014:Pneumonia / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000502:physiology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000502:physiology; D013931:Thromboxanes / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology
D010972:Platelet Activating Factor; D013931:Thromboxanes; D015936:Complement C5a