Chemotactic factors stimulate CD18-dependent canine neutrophil adherence and motility on lung fibroblasts

Alan R. Burns, Scott I. Simon, Gilbert L. Kukielka, Judith L. Rowen, Huifang Lu, Leonardo H. Mendoza, Evelyn S. Brown, Mark L. Entman, C. Wayne Smith

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The mechanisms by which neutrophils migrate through the alveolar interstitium during acute lung inflammation are unknown. We wished to determine whether platelet-activating factor (PAF) and IL-8, two important mediators in neutrophil transendothelial migration, stimulated neutrophil adherence and motility on lung fibroblasts. Canine fibroblasts grown from lung explants were characterized by light and electron microscopy, and flow cytometry. Unstimulated neutrophils adhered poorly (<2%) to cultured fibroblasts. However, neutrophils stimulated with PAF (20-200 nM) showed a dose-dependent increase in adherence that was largely (70%) mediated by the β2 (CD11/CD18) integrins; adherence was less dependent (50%) on fibroblast intercellular adhesion molecule-1. Conversely, neutrophils stimulated with canine rIL-8 did not increase their adherence to fibroblasts. PAF-stimulated neutrophils were nonmotile on the surface of the fibroblast, but subsequent addition of rIL-8 (10-8 M) induced motility that was entirely CD18 dependent. Fibroblasts stimulated with human rTNF-α or Escherichia coli endotoxin (LPS) were a significant source of IL-8 mRNA. In response to rTNF- α (50 U/ml), IL-8 mRNA was detected at 2 h by Northern blot analysis; it peaked at 6 h and returned to baseline by 24 h. Fibroblasts stimulated with rTNF-α secreted IL-8 protein into the culture medium; secreted IL-8 was chemotactic for neutrophils. These data suggest that fibroblasts can function not only as an adhesive substrate, but also as a source of stimulation for neutrophil migration through the inflamed alveolar interstitium.

Original languageEnglish (US)
Pages (from-to)3389-3401
Number of pages13
JournalJournal of Immunology
Volume156
Issue number9
StatePublished - May 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Burns, A. R., Simon, S. I., Kukielka, G. L., Rowen, J. L., Lu, H., Mendoza, L. H., Brown, E. S., Entman, M. L., & Smith, C. W. (1996). Chemotactic factors stimulate CD18-dependent canine neutrophil adherence and motility on lung fibroblasts. Journal of Immunology, 156(9), 3389-3401.