Mast Cells Modulate Acute Ozone-induced Inflammation of the Murine Lung

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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 (NBB6F1-W/Wv WCB6F1-SI/SId) and bone-marrow-transplanted W/WV 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/WV and SI/SId 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/WV mice by transplantation of bone marrow cells from congenic + / + mice, and O3-induced lung inflammation was assessed in the mast-cell-replete W/WV mice. After O3 exposure, the changes in lavageable PMNs and total protein of mast-cell-replete W/WV mice were not different from age-matched normal + / + control mice, and they were significantly greater than those of sham-transplanted W/WV 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.

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