GcGlobulin functions as a cochemotaxin in the lower respiratory tract: A potential mechanism for lung neutrophil recruitment in cigarette smokers

J. P. Metcalf, A. B. Thompson, G. L. Gossman, K. J. Nelson, S. Koyama, S. I. Rennard, R. A. Robbins

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Activation of the complement pathway with generation of the potent chemotaxin C5a may play a significant role in the neutrophil accumulation seen in the lungs of patients with smoking-associated disease. Although C5a is rapidly degraded to the less potent chemotaxin C5a des Arg, binding of this peptide with its cochemotaxin Gcglobulin (GcG) can restore its chemotactic potency. Therefore, modulation of Gcglobulin levels in smoking-induced lung disease could affect the accumulation of neutrophils seen in this disorder. To test this hypothesis GcG was measured by an enzyme-linked immunosorbent assay in bronchoalveolar lavage fluids (BALF) obtained from nonsmokers, asymptomatic smokers, and patients with chronic obstructive pulmonary disease (COPD). Antigenic amounts of GcG in BALF were increased in COPD patients and asymptomatic smokers compared with nonsmokers (6.35 ± 1.02 and 5.15 ± 1.07 versus 2.82 ± 0.37 μg/mg albumin, p < 0.05). In addition, we found that BALF enhanced C5a des Arg-mediated chemotaxis (48.3 ± 5.6 versus 11.2 ± 1.6 cells/high power field, p < 0.05), an effect that was not seen in the presence of GcG antibody. Furthermore, BALF GcG was similar to serum GcG using Western blot analysis, and the interaction of GcG with C5a des Arg was not inhibited by cigarette smoke. These data demonstrate that elevation of BALF GcG levels occurs in smoking-associated lung disease and that this protein is biologically active and capable of increasing C5a des Arg-mediated chemotaxis. This suggests that modulation of GcG levels may be important in smoking-associated lung diseases.

Original languageEnglish (US)
Pages (from-to)844-849
Number of pages6
JournalAmerican Review of Respiratory Disease
Volume143
Issue number4 I
DOIs
StatePublished - 1991

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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