Role of cytokine-induced neutrophil chemoattractant (CINC) in ozone-induced airway inflammation and hyperresponsiveness

Am J Respir Crit Care Med. 1997 Jul;156(1):234-9. doi: 10.1164/ajrccm.156.1.9606095.

Abstract

Cytokine-induced neutrophil chemoattractant (CINC) is a rat chemokine with potent chemoattractant effects on neutrophils. We determined the involvement of CINC in ozone-induced airway neutrophilia and bronchial hyperresponsiveness (BHR) in the rat. We found a marked increase in lung CINC messenger RNA (mRNA) within 2 h after cessation of ozone exposure (1 ppm for 3 h), as measured by Northern blot analysis, whereas rats exposed to room air had no detectable CINC mRNA. Ozone exposure induced a significant neutrophilia in bronchoalveolar lavage fluid (BALF) at 24 h after exposure (air-exposed rats: 4.2 +/- 2.0 x 10(4), versus ozone-exposed rats: 16.1 +/- 3.7 x 10(4)); prior treatment with a goat anti-CINC antibody (1 mg, intravenously) suppressed the neutrophilia (3.1 +/- 0.9 x 10(4)). When administered intratracheally, the antibody (230 micrograms) partially inhibited the influx of neutrophils. The increase in bronchial responsiveness to acetylcholine observed after ozone exposure was not inhibited by the anti-CINC antibody. The anti-CINC antibody (1 mg, intravenously) also inhibited BALF neutrophilia induced by exposure to a higher concentration of ozone (3 ppm, 3 h), without an effect on BHR. CINC is an important chemokine causing ozone-induced neutrophil chemoattraction, but is not involved in the induction of ozone-induced BHR. The neutrophil is unlikely to contribute to BHR in this model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Antibodies
  • Bronchial Hyperreactivity / chemically induced
  • Bronchial Hyperreactivity / immunology*
  • Chemokines / immunology
  • Chemokines, CXC*
  • Chemotactic Factors / genetics
  • Chemotactic Factors / immunology
  • Chemotactic Factors / physiology*
  • Growth Substances / genetics
  • Growth Substances / immunology
  • Growth Substances / physiology*
  • Inflammation / chemically induced
  • Intercellular Signaling Peptides and Proteins*
  • Male
  • Neutrophils / drug effects*
  • Ozone / pharmacology*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Inbred BN

Substances

  • Antibodies
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Ozone
  • Acetylcholine