Role of protein synthesis and CD 11 /CD 18 adhesion complex in neutrophil emigration into the lung

Robert K. Winn, William J. Mileski, Nicholas L. Kovach, Claire M. Doerschuk, Charles L. Rice, John M. Harlan

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The mechanism of neutrophil (PMN) emigration into the lung may he stimulus-dependent. This study examined PMN emigration in the lung induced by intratracheal instillation of lipopolysaccharide (LPS), Streptococcus pneumoniae (S. pneu) organisms, supernatant from S. pneu incubated with alveolar macrophages (AMF{cyrillic} Escherichia coli (E. coli) organisms, or phorhol myristate acetate (PMA). Rabbits were pre-treated with either the CD18 monoclonal antibody (MAb) 60.3, the protein synthesis inhibitor cycloheximide (Cx), or, in one case, both. Animals were then given one of the above stimuli to elicit PMN emigration. Four hours after the stimulus was instilled, animals were killed and total and differential cell counts were performed on bronchoal-veolar lavage (BAL) fluid. PMN emigration in response to PMA was virtually abolished by MAb 60.3, but was not significantly inhibited by Cx. Emigration induced by LPS was inhibited by 80% by either MAb 60.3 or Cx, and greater than 94% when MAb 60.3 and Cx were given simultaneously. Emigration in response to E. coli organisms was 80% inhibited by MAb 60.3. Emigration induced by S. pneu was approximately 50% inhibited by MAb 60.3, but was greater than 90% blocked by Cx. The MAb 60.3 had approximately the same effect on PMN emigration toward the supernatant from co-incubation of AMF{cyrillic} with S. pneu as it did toward live S. pneu. It is concluded that the mechanism of PMN emigration into the lung is stimulus-dependent. The CD18-dependent mechanism is responsible for the majority of the emigration in response to PMA, E. coli LPS, and E. coli organisms. S. pneu and supernatant from S. pneu + AMF{cyrillic} produce a CD18-independent pathway. These data suggest the requirement for de novo protein synthesis for PMN emigration in response to LPS and S. pneu, but not for PMA-induced emigration.

Original languageEnglish (US)
Pages (from-to)221-235
Number of pages15
JournalExperimental Lung Research
Volume19
Issue number2
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

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