Role of cytokine-induced neutrophil chemoattractant (CINC) in ozone-induced airway inflammation and hyperresponsiveness.
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.
Koto
H
H
Department of Thoracic Medicine, Imperial College of Science, Technology and Medicine, London, England.
Salmon
M
M
Haddad el-B
Huang
T J
TJ
Zagorski
J
J
Chung
K F
KF
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000906:Antibodies; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology*; D018925:Chemokines / Q000276:immunology; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006133:Growth Substances / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007249:Inflammation / Q000139:chemically induced; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D010126:Ozone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011914:Rats, Inbred BN
D000906:Antibodies; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D010126:Ozone; D000109:Acetylcholine