Acid instillation enhances the inflammatory response to subsequent lipopolysaccharide challenge in rats

Citation
H. Yamada et al., Acid instillation enhances the inflammatory response to subsequent lipopolysaccharide challenge in rats, AM J R CRIT, 162(4), 2000, pp. 1366-1371
Citations number
32
Categorie Soggetti
Cardiovascular & Respiratory Systems","da verificare
Journal title
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
ISSN journal
1073449X → ACNP
Volume
162
Issue
4
Year of publication
2000
Pages
1366 - 1371
Database
ISI
SICI code
1073-449X(200010)162:4<1366:AIETIR>2.0.ZU;2-E
Abstract
Aspiration of gastric contents is one of leading causes of the acute respir atory distress syndrome (ARDS). The pathogenesis of acid aspiration-induced acute lung injury is well understood. Less clear is why patients who have suffered acid aspiration are susceptible to ARDS. We studied the effects of acid instillation on the inflammatory response to subsequent lipopolysacch aride (LPS) challenge in rats. Instillation of acid into the right lung wor sened the pathology induced by LPS that was administered 24 h after acid in stillation. This included worsened oxygenation, increased pulmonary edema, increased production of tumor necrosis factor-alpha (TNF-alpha) and cytokin e-induced neutrophil chemoattractant, neutrophil accumulation and mobilizat ion to the alveolar spaces, and nitric oxide (NO) production. Of interest, neutrophil mobilization, NO production, and protein permeability were also magnified in the left lung. These effects were attenuated by administration of the protein tyrosine kinase (PTK) inhibitors genistein and tyrphostin A G556. These data suggest that acid instillation primes the rat to enhance t he inflammatory response to subsequent endotoxin challenge and that at leas t part of the augmented inflammatory response depends on PTK.