PNEUMOCYSTIS-CARINII INFECTION ALTERS GTP-BINDING PROTEINS IN THE LUNG

The GTP-binding regulatory proteins (G proteins) in the membranes of t he lung parenchyma from normal, uninfected ferrets were compared to th ose from immunosuppressed animals with and without Pneumocystis carini i pneumonitis. In lung membranes, pertussis toxin (PT) catalyzed ADP r ibosylation of a 41-kDa protein; treatment with cholera toxin (CT) led to ribosylation of a 44-kDa polypeptide. Compared to that in the norm al ferrets, the level of the 44-kDa protein was dramatically suppresse d in the P. carinii-infected animals. Western blot analysis with speci fic antibodies to a(s) (which recognized CT substrates), alpha(common) (which reacted to PT substrates), the alpha(q/11) epitope, and the be ta subunit demonstrated that these proteins were decreased in animals with P. carinii pneumonitis (PCP). Western blotting of PCP-free membra nes with a pan-Ras antibody revealed a 21-kDa polypeptide (correspondi ng to small G proteins). The level of the 21-kDa protein in membranes from PCP-affected animals was only 30% of that in membranes from PCP-f ree animals. Finally, analogous studies performed with rat lung membra nes revealed similar findings. These data suggest that, independent of its exacerbation of immunosuppression, PCP leads to extensive changes in the GTP-binding proteins in the lung.