Enhanced Ia expression by alveolar macrophages following intratracheal administration of bleomycin to rats

Bleomycin is an important anticancer drug that causes severe, and sometimes life-threatening, pulmonary toxicity. Initially, there is an acute inflammation followed by an irreversible pulmonary fibrosis. Our studies have focussed on the effects of the acute pulmonary inflammation on the state of alveolar macrophage activation. To study this, we administered a single dose of 3.6 mg bleomycin/kg body weight intratracheally to rats and obtained alveolar macrophages at selected times thereafter. Ia expression was determined by fluorescent microscopy of cells labelled with a fluorochrome-tagged antibody against rat Ia molecules. We report that: 1.) alveolar macrophages have elevated Ia expression shortly after receiving intratracheally administered bleomycin; 2.) Ia expression is not limited to a specific subpopulation of alveolar macrophages; 3.) Ia expression is transient in nature returning to control levels 7-14 days after bleomycin administration; and, 4.) the degree of upregulation of Ia expression is directly related to the dose of bleomycin administered.