Prostaglandin E1 attenuates cytotoxic mechanisms of primed neutrophils

Shock
D Y TamuraC C Silliman

Abstract

In a recent clinical trial, liposomal prostaglandin E1 (PGE1) improved oxygenation, increased compliance, and decreased ventilator dependency in patients with adult respiratory distress syndrome (ARDS), thus renewing interest in PGE1 as a potential modulator of inflammation. The neutrophil (PMN) is believed to play a key role in the development of ARDS. Consequently, we investigated the effects of PGE1 on three components of the neutrophil inflammatory response: reactive oxygen species (ROS) generation, protease release, and surface expression of adhesion molecules. Human neutrophils were incubated with PGE1 and then primed with platelet-activating factor (PAF) and activation with N-formyl-methionyl-leucylphenylalanine (fMLP). PGE1 at a dose range of (10[-8] to 10[-5] M) attenuated primed/activated (PAF/fMLP) PMN superoxide anion generation and elastase release. In contrast, PGE1 doses > or =10[-5] M were required to attenuate PAF-stimulated neutrophil upregulation of CD11b/CD18 adhesion molecules. PGE1 also diminished the duration of the PAF-induced cytosolic calcium (Ca2+) flux. Our results suggest that plasma levels of PGE1 attained in patients with ARDS may attenuate ROS and protease neutrophil cytotoxicity but may not effe...Continue Reading

Citations

Apr 29, 2006·The Japanese Journal of Thoracic and Cardiovascular Surgery : Official Publication of the Japanese Association for Thoracic Surgery = Nihon Kyōbu Geka Gakkai Zasshi·Tetsuro SanoHisataka Yasui
Sep 29, 2000·Critical Care Medicine·R C McIntyreE Abraham
Dec 27, 2005·Journal of the American College of Surgeons·Rohan N LallRaul Coimbra
Mar 10, 2001·AACN Clinical Issues·M H van SoerenW M Haddara

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