Protective effects of prostaglandin E1 on acute lung injury of caerulein-induced acute pancreatitis in rats.
Infusion of a supramaximally stimulating dose of the pancreatic secretagogue caerulein (10 micrograms.kg-1.h-1) for 4 h induces interstitial edematous acute pancreatitis in rats. This model of acute pancreatitis is associated with evidence of acute lung injury, including sequestered neutrophils within the pulmonary microvasculature, increased microvascular permeability, and interstitial pulmonary edema. Infusion of prostaglandin E1 (PGE1; 50 ng.kg-1.min-1) along with caerulein does not alter the severity of secretagogue-induced pancreatitis, but it does reduce the severity of pancreatitis-associated acute lung injury. The rise in lung weight, lung water content, and pulmonary microvascular permeability and the sequestration of neutrophils within the pulmonary microvasculature that accompany secretagogue-induced pancreatitis are all reduced by infusion of PGE1. Infusion of PGE1 does not interfere with polymorphonuclear neutrophil sequestration in the pancreas or reduce the enhanced expression of CD11b/c receptors on circulating neutrophils. Our observations indicate that PGE1 reduces the severity of pancreatitis-associated acute lung injury by preventing neutrophil sequestration within the lung. We speculate that PGE1 interferes with neutrophil sequestration by dilating pulmonary vasculature, increasing pulmonary flow rate, and reducing neutrophil-endothelial cell interaction and attachment.
Yamanaka
K
K
Department of Surgery, Beth Israel Hospital, Boston, Massachusetts, USA.
Saluja
A K
AK
Brown
G E
GE
Yamaguchi
Y
Y
Hofbauer
B
B
Steer
M L
ML
D000208:Acute Disease; D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D002108:Ceruletide; D016167:Integrin alphaXbeta2 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology* / Q000517:prevention & control*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced* / Q000150:complications* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D016167:Integrin alphaXbeta2; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D002108:Ceruletide; D000527:Alprostadil