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

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23 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume260
Issue number2 29-2
StatePublished - 1991

Fingerprint

leucyl-phenylalanine
Endotoxins
Lipopolysaccharides
Neutrophils
Lung Injury
Lung
Vinblastine
Albumins
Tungsten
Xanthine Oxidase
Oxidoreductases
Molybdenum

Keywords

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

ASJC Scopus subject areas

  • Physiology

Cite this

Anderson, B. O., Bensard, D. D., Brown, J. M., Repine, J. E., Shanley, P. F., Leff, J. A., ... Harken, A. H. (1991). FNLP injures endotoxin-primed rat lung by neutrophil-dependent and -independent mechanisms. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 260(2 29-2).

FNLP injures endotoxin-primed rat lung by neutrophil-dependent and -independent mechanisms. / Anderson, B. O.; Bensard, D. D.; Brown, J. M.; Repine, J. E.; Shanley, P. F.; Leff, J. A.; Terada, L. S.; Banerjee, A.; Harken, A. H.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 260, No. 2 29-2, 1991.

Research output: Contribution to journalArticle

Anderson, BO, Bensard, DD, Brown, JM, Repine, JE, Shanley, PF, Leff, JA, Terada, LS, Banerjee, A & Harken, AH 1991, 'FNLP injures endotoxin-primed rat lung by neutrophil-dependent and -independent mechanisms', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol. 260, no. 2 29-2.
Anderson, B. O. ; Bensard, D. D. ; Brown, J. M. ; Repine, J. E. ; Shanley, P. F. ; Leff, J. A. ; Terada, L. S. ; Banerjee, A. ; Harken, A. H. / FNLP injures endotoxin-primed rat lung by neutrophil-dependent and -independent mechanisms. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 1991 ; Vol. 260, No. 2 29-2.
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AU - Bensard, D. D.

AU - Brown, J. M.

AU - Repine, J. E.

AU - Shanley, P. F.

AU - Leff, J. A.

AU - Terada, L. S.

AU - Banerjee, A.

AU - Harken, A. H.

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N2 - 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.

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