Ozone inhalation stimulates expression of a neutrophil chemotactic protein, macrophage inflammatory protein 2

Toxicol Appl Pharmacol. 1993 Apr;119(2):306-9. doi: 10.1006/taap.1993.1074.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Animals
  • Base Sequence
  • Chemokine CXCL2
  • Cytokines / drug effects*
  • Cytokines / genetics
  • Gene Expression / drug effects
  • Glyceraldehyde-3-Phosphate Dehydrogenases / drug effects
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Hydrogen Peroxide / pharmacology
  • In Vitro Techniques
  • Macrophages, Alveolar / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Monokines / drug effects*
  • Monokines / genetics
  • Ozone / administration & dosage
  • Ozone / pharmacology*
  • Peptide Fragments / drug effects
  • Peptide Fragments / genetics
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Rats
  • Rats, Inbred F344


  • Chemokine CXCL2
  • Cytokines
  • Monokines
  • Peptide Fragments
  • RNA, Messenger
  • glyceraldehyde 3-phosphate dehydrogenase (304-313)
  • Ozone
  • Hydrogen Peroxide
  • Glyceraldehyde-3-Phosphate Dehydrogenases