Murine hypersensitivity pneumonitis: evidences for the role of eicosanoids and platelet activating factor

Eicosanoids and platelet activating factor (PAF) are involved in numerous lung diseases. However, few studies have looked for their role in hypersensitivity pneumonitis (HP). HP was induced in mice by repeated instillations of Saccharapolyspora rectivirgula (Micropolyspora faeni) during 3 weeks. Bronchoalveolar lavages (BAL) were performed each week. BAL macrophage, lymphocyte and neutrophil counts increased at week 1, for a maximal increase after 3 weeks. Production of LTB4, LTC4, PGE2 and TXB2 by alveolar macrophages stimulated in vitro with calcium ionophore was maximal after 3 weeks, the appearance of PGE2 and TXB2 preceding that of LTB4 and LTC4. Eicosanoid production by AM correlated with BAL cell counts. To look for the importance of PAF in the development of experimental HP, mice were treated with BN52021 and BN50730, two PAF antagonists, and BAL were performed after 3 weeks of treatment. The compounds BN52021 and BN50730 reduced total BAL cell counts (x 10(5) cells/ml) in animals treated with S. rectivirgula from 8.4 +/- 0.8 to 4.4 +/- 1.1 and 3.7 +/- 0.2 respectively. BAL cell numbers in control animals were 0.4 +/- 0.1. In conclusion, eicosanoids are increased in experimental HP, and, as PAF, could play a role in the accumulation of alveolar cells.