Effects of RU 41740 aerosol treatment on mouse bronchoalveolar cells, and protection afforded against influenza virus infection

Abstract

RU 41740, an immunomodulating compound extracted from Klebsiella pneumoniae, was previously shown to enhance mice resistance to bacterial and viral lung infections. To explore lung defense mechanisms, we studied the influence of RU 41740 aerosol treatment on the bronchoalveolar cell populations. Five successive daily RU 41740 aerosol treatments induced a large accumulation of leukocytes in the lungs 4h after the last treatment. Polymorphonuclear leukocytes predominated. The numbers of lymphocytes and monocytes rose significantly. A single RU 41740 aerosol treatment significantly raised the number of polymorphonuclears only. A luminol-dependent chemiluminescence assay was used to test the effect of RU 41740 on the opsonized zymosan induced response of alveolar macrophages. In vitro, addition of RU 41740 enhanced this chemiluminescence. After a single RU 41740 aerosol treatment of mice, the chemiluminescence of purified alveolar macrophages from these mice increased significantly. The protective effect of five daily RU 41740 aerosol treatments against influenza virus infection was believed to be due to the great intensity of the cellular response and the polymorphonuclear influx. The alveolar macrophage activation observed might also explain the enhanced resistance of mice to influenza virus infection.