Plasminogen activator production in a rat model of Pneumocystis carinii pneumonia

Several studies have indicated that the serine protease urokinase-plasminog en-activator (uPA) is an important factor in host defense against pulmonary pathogens. To gain a better insight into the role of uPA in Pneumocystis c arinii (P carinii) pneumonia (PCP), we evaluated PA production in alveolar macrophages (AMs) obtained from rats with steroid-induced PCP. Treatment wi th cortisone acetate favored PCP in 91% of rats. In the bronchoalveolar lav age (BAL) samples of immunosuppressed rats both with and without PCP, we ob served a decrease in uPA activity as well as a decrease in cell number. Uro kinase-PA production by AMs was reduced in rats treated with cortisone alon e. However, an increase in cell-associated uPA was observed in rats with PC P. This increase appears to be produced in response to P carinii infection. In fact, when AMs obtained from untreated healthy or immunosuppressed unin fected rats were challenged with P carinii, a significant increase in PA ac tivity in cell lysates was observed, though a lower response was obtained i n cortisone-treated animals. Our results suggest that healthy AMs respond t o the presence of R carinii with an increase in uPA production and that thi s response in immunodepressed rat-AMs is partially impaired.