Ozone inhalation stimulates expression of a neutrophil chemotactic protein, macrophage inflammatory protein 2.
Short-term exposure of humans and animals to ozone results in increased lung neutrophils; however, the mechanisms underlying this response are not completely understood. We examined the potential involvement of the neutrophil chemotactic factor, macrophage inflammatory protein 2 (MIP-2), in ozone-induced inflammation. Exposure-response relationships for ozone and MIP-2 expression were characterized by exposing C57B1/6 mice to 0.1-2 ppm ozone for 3 hr and determining lung levels of MIP-2 mRNA 6 hr after exposure. Temporal relationships between ozone and MIP-2 were determined by exposing mice (2 ppm ozone x 3 hr) and characterizing MIP-2 mRNA expression 0, 2, 6, and 24 hr after exposure. Neutrophils in lung lavage fluid were determined in both exposure-response and time course studies. Ozone concentrations > or = 1.0 ppm increased MIP-2 mRNA and this increase corresponded with recruitment of neutrophils. MIP-2 mRNA was increased immediately after ozone exposure and decreased to control levels by 24 hr. To examine the role of direct oxidant effects in ozone-induced MIP-2 expression, alveolar macrophages were exposed in vitro for 4 hr to 10(-10)-10(-5) M hydrogen peroxide and MIP-2 expression was characterized. MIP-2 mRNA levels in lung macrophages were increased by > or = 10(-9) M hydrogen peroxide. In summary, our findings suggest the chemotactic protein MIP-2 may be responsible, at least in part, for ozone-induced increases in lung neutrophils and indicate that direct exposure of alveolar macrophages to an oxidant is sufficient to induce MIP-2 expression.
Driscoll
K E
KE
Human Safety Department, Procter & Gamble Company, Cincinnati, Ohio 45239.
Simpson
L
L
Carter
J
J
Hassenbein
D
D
Leikauf
G D
GD
D000280:Administration, Inhalation; D000818:Animals; D001483:Base Sequence; D054426:Chemokine CXCL2; D016207:Cytokines / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000187:drug effects / Q000235:genetics; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D016676:Macrophages, Alveolar / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D015846:Monokines / Q000187:drug effects* / Q000235:genetics; D010126:Ozone / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000187:drug effects / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344
D054426:Chemokine CXCL2; D016207:Cytokines; D015846:Monokines; D010446:Peptide Fragments; D012333:RNA, Messenger; C068142:glyceraldehyde 3-phosphate dehydrogenase (304-313); D010126:Ozone; D006861:Hydrogen Peroxide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases