Virus-induced increases in bronchiolar mast cells in Brown Norway rats are associated with both local mast cell proliferation and increases in blood mast cell precursors.

BACKGROUND

Parainfluenza type 1 (Sendai) virus-induced bronchiolitis during early life in rats induces increases in bronchiolar mast cells that persist for months after infection and are associated with airway obstruction and airway hyperresponsiveness. Brown Norway (BN) rats are highly susceptible, and Fischer 344 (F344) rats are relatively resistant to, Sendai virus-induced increases in airway responsiveness and mast cell density.

EXPERIMENTAL DESIGN

To identify mechanisms responsible for the virus-induced mast cell increases, BN rats were studied using in vivo bromodeoxyuridine labeling, in vitro culture of bone marrow, blood, and lung mast cell progenitors (colony-forming unit-mast cell (CFU-MC)), and in vivo treatment with the rodent mast cell stabilizers disodium cromoglycate and nedocromil sodium. Bone marrow, blood, and lung CFU-MC were also quantitated in F344 rats.

RESULTS

At 10 days after inoculation, there was a fivefold increase (p = 0.001) in the bromodeoxyuridine labeling index of bronchiolar mast cells in virus-inoculated BN rats. Viral inoculation increased CFU-MC/ml blood greater than fivefold (p < 0.05) in BN rats at 10 days after inoculation, and BN rats had greater numbers of both blood and lung CFU-MC than did F344 rats. Treatment with inhibitors of mast cell degranulation had no effect on Sendai virus-induced bronchiolar mast cell increases in BN rats.

CONCLUSIONS

Virus-induced increases in bronchiolar mast cells result from proliferation of preexisting mast cells and may be augmented by recruitment of circulating mast cell precursors.