Mast cells modulate acute ozone-induced inflammation of the murine lung

S. R. Kleeberger, J. E. Seiden, R. C. Levitt, L. Y. Zhang

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

We hypothesized that mast cells modulate lung inflammation that develops after acute ozone (O3) exposure. Two tests were done: (1) genetically mast- cell-deficient (WBB6F1-W/W(v), WCB6F1-SI/SI(d)) and bone-marrow- transplanted W/W(v) mice were exposed to O3 or filtered air, and the inflammatory responses were compared with those of mast-cell-sufficient congenic mice (WBB6F1-+/+, WCB6F1-+/+); (2) genetically O3-susceptible C57BL/6J mice were treated pharmacologically with putative mast-cell modulators or vehicle, and the O3-induced inflammatory responses were compared. Mice were exposed to 1.75 ppm O3 or air for 3 h, and lung inflammation was assessed by bronchoalveolar lavage (BAL) 6 and 24 h after exposure. Relative to O3-exposed W/W(v) and SI/SI(d) mice, the mean numbers of lavageable polymorphonuclear leukocytes (PMNs) and total BAL protein concentration (a marker of permeability) were significantly greater in the respective O3-exposed normal congenic +/+ mice (p < 0.05). Mast cells were reconstituted in W/W(v) mice by transplantation of bone marrow cells from congenic +/+ mice, and O3-induced lung inflammation was assessed in the mast-cell-replete W/W(v) mice. After O3 exposure, the changes in lavageable PMNs and total protein of mast-cell-replete W/W(v) mice were not different from age-matched normal +/+ control mice, and they were significantly greater than those of sham-transplanted W/W(v) mice (p < 0.05). Genetically susceptible C57BL/6J mice were pretreated with a mast-cell stabilizer (nedocromil sodium), secretagogue (compound 48/80), or vehicle, and the mice were exposed to O3. Relative to vehicle controls, both drugs significantly attenuated the O3-induced influx of PMNs (p < 0.05), and nedocromil significantly reduced the change in BAL protein elicited by O3 exposure (p < 0.05). Results suggest that mast cells modulate the influx of PMNs and the change in murine lung permeability induced by acute exposure to O3.

Original languageEnglish (US)
Pages (from-to)1284-1291
Number of pages8
JournalAmerican Review of Respiratory Disease
Volume148
Issue number5
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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