Endotoxin stimulates bronchial epithelial cells to release chemotactic factors for neutrophils: A potential mechanism for neutrophil recruitment, cytotoxicity, and inhibition of proliferation in bronchial inflammation

S. Koyama, Stephen I. Rennard, G. D. Leikauf, S. Shoji, S. Von Essen, L. Claassen, R. A. Robbins

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

To test the effect of endotoxin on bronchial epithelial cells (BEC), BEC were isolated from bovine lungs and cultured in the presence of bacterial endotoxin. The BEC culture supernatant fluids were harvested, and neutrophil chemotactic activity (NCA) was determined with a blindwell chamber technique; cytotoxicity determined by lactate dehydrogenase release and BEC proliferation determined by Coulter counting. Endotoxin caused a dose- and time-dependent release of NCA from BEC cultures compared with media alone (82.3 ± 8.1 vs 12.0 ± 3.1 cells/high power field, p < 0.001). To further characterize this activity, reverse phase HPLC analysis of released eicosanoid metabolites after [3H]arachidonic acid incorporation was performed. Endotoxin stimulated the release of the neutrophil chemoattractants, leukotriene B4 and 12-hydroxyeicosatetraenoic acids. Endotoxin also resulted in a dose and time dependent release of lactate dehydrogenase (42.9 ± 4.2 vs 20.2 ± 2.2 U/liter, p < 0.001) although higher doses were required to cause cytotoxicity than to stimulate chemotaxis. Finally, endotoxin resulted in a dose dependent inhibition of BEC proliferation (176 x 103 ± 16 x 103 vs 1,080 x 103 ± 38 x 103 cells/ml measured at day 14, p < 0.001). These data suggest that bacterial release of endotoxin may contribute to the pathophysiologic changes observed in bronchial inflammation by stimulating BEC to release NCA, denuding airway epithelium by causing cytotoxicity of BEC, and inhibiting epithelial repair by inhibiting BEC proliferation.

Original languageEnglish (US)
Pages (from-to)4293-4301
Number of pages9
JournalJournal of Immunology
Volume147
Issue number12
StatePublished - 1991

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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