Differential expression of platelet-activating factor acetylhydrolase in lung macrophages
- 1 December 2009
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Lung Cellular and Molecular Physiology
- Vol. 297 (6), L1141-L1150
- https://doi.org/10.1152/ajplung.00022.2009
Abstract
Platelet-activating factor (PAF) acetylhydrolase plays a crucial role inactivating the potent inflammatory mediator, PAF. PAF is implicated in the initiation and propagation of acute lung injury. Although PAF acetylhydrolase is a constitutively active plasma protein, increased PAF production during inflammatory events may necessitate an increase in PAF acetylhydrolase activity in the local environment. A series of experiments were conducted to determine whether the systemic administration of LPS to Sprague-Dawley rats resulted in enhanced expression of PAF acetylhydrolase in lung tissue. Ribonuclease protection assays revealed a dramatic increase in PAF acetylhydrolase mRNA, which peaked at 24 h following in vivo LPS administration. The increase in PAF acetylhydrolase mRNA was dose dependent and was detected when as little as 10 μg/kg of LPS was administered. Western blot analyses of lung tissue homogenates confirmed an increased production of PAF acetylhydrolase protein in response to LPS. In addition, Western blot analyses revealed the rat PAF acetylhydrolase protein exhibited heterogeneous molecular weights with predominant species migrating at 63 and 67 kDa. Some of the molecular weight heterogeneity likely resulted from extensive glycosylation of the secreted protein. Immunohistochemical analyses of lung tissue sections and colocalization experiments revealed a heterogenous population of cells that express the plasma-type PAF acetylhydrolase. Lung interstitial macrophages were PAF acetylhydrolase positive, but surprisingly, alveolar macrophages did not increase expression of PAF acetylhydrolase in response to systemic LPS administration. In addition, rat granulocytes consisting primarily of neutrophils were strongly positive for PAF acetylhydrolase in the LPS-exposed lung tissue. The absence of immunoreactive PAF acetylhydrolase in alveolar macrophages obtained from bronchial alveolar lavage confirmed that systemic LPS administration resulted in enhanced PAF acetylhydrolase expression only in a subset of lung macrophages.This publication has 51 references indexed in Scilit:
- Molecular basis for susceptibility of plasma platelet‐activating factor acetylhydrolase to oxidative inactivationThe FASEB Journal, 2007
- Plasma platelet-activating factor acetylhydrolase activity in critically ill patients*Critical Care Medicine, 2005
- Platelet-activating factor acetylhydrolase is increased in lung lavage fluid from patients with acute respiratory distress syndromeCritical Care Medicine, 2003
- The pan-chemokine inhibitor NR58-3.14.3 abolishes tumour necrosis factor-alpha accumulation and leucocyte recruitment induced by lipopolysaccharide in vivoImmunology, 2001
- The Expression and Localization of Plasma Platelet-activating Factor Acetylhydrolase in Endotoxemic RatsOnline Journal of Public Health Informatics, 2000
- Cellular Source(s) of Platelet-Activating-Factor Acetylhydrolase Activity in PlasmaBiochemical and Biophysical Research Communications, 1999
- Oxygen radicals inhibit human plasma acetylhydrolase, the enzyme that catabolizes platelet-activating factor.JCI Insight, 1994
- Metabolism of Platelet Activating Factor in LungAnnals of the New York Academy of Sciences, 1991
- Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitisThe Journal of Pediatrics, 1990
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970