FNLP injures endotoxin-primed rat lung by neutrophil-dependent and -independent mechanisms

B. O. Anderson, D. D. Bensard, J. M. Brown, J. E. Repine, P. F. Shanley, J. A. Leff, L. S. Terada, A. Banerjee, A. H. Harken

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Bacterial lipopolysaccharide (LPS) and an N-formyl peptide, N-formyl-neoleucyl-leucyl-phenylalanine (FNLP), synergistically promote lung injury in rats as measured by 125I-labeled albumin flux. Concomitantly, neutrophils are sequestered in the lung. We hypothesized that LPS-FNLP-induced lung injury is mediated both by neutrophil-dependent and -independent mechanisms. Rats were depleted of circulating and marginating neutrophils with vinblastine. LPS-FNLP-induced lung protein leak was partially decreased in these neutrophil-depleted animals, although a component of lung injury remained. We hypothesized that LPS-FNLP-induced lung injury was also mediated by xanthine oxidase (XO). Rats were fed a tungsten-enriched diet that inactivates molybdenum-dependent oxidase systems. LPS-FNLP-induced lung leak was partially decreased in these animals as well. When tungsten-fed rats were also neutrophil depleted with vinblastine, no increase in 125I-albumin flux was observed in response to LPS-FNLP. In parallel experiments, lungs from vinblastine-pretreated rats were isolated and perfused. FNLP infusion into the LPS-primed, crystalloid-perfused lungs caused increased 125I-albumin flux, which was prevented by oxidase inhibition. We conclude that LPS-FNLP-induced lung injury is both neutrophil mediated and neutrophil independent. The nonneutrophil component of the LPS-FNLP-induced lung injury appears to be pulmonary XO derived and dependent.

Original languageEnglish (US)
Pages (from-to)R413-R420
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume260
Issue number2 29-2
StatePublished - Jan 1 1991

Keywords

  • Endothelial cell
  • N-formyl-neoleucyl-leucyl-phenylalanine
  • Neutrophil depletion
  • Primed activation
  • Synergy
  • Xanthine oxidase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'FNLP injures endotoxin-primed rat lung by neutrophil-dependent and -independent mechanisms'. Together they form a unique fingerprint.

Cite this