Pneumocystis carinii infection alters GTP-binding proteins in the lung.
The GTP-binding regulatory proteins (G proteins) in the membranes of the lung parenchyma from normal, uninfected ferrets were compared to those from immunosuppressed animals with and without Pneumocystis carinii pneumonitis. In lung membranes, pertussis toxin (PT) catalyzed ADP ribosylation of a 41-kDa protein; treatment with cholera toxin (CT) led to ribosylation of a 44-kDa polypeptide. Compared to that in the normal ferrets, the level of the 44-kDa protein was dramatically suppressed in the P. carinii-infected animals. Western blot analysis with specific antibodies to alpha s (which recognized CT substrates), alpha common (which reacted to PT substrates), the alpha q/11 epitope, and the beta subunit demonstrated that these proteins were decreased in animals with P. carinii pneumonitis (PCP). Western blotting of PCP-free membranes with a pan-Ras antibody revealed a 21-kDa polypeptide (corresponding 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-free animals. Finally, analogous studies performed with rat lung membranes 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.
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Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Hughes
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WT
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D004271:DNA, Fungal / Q000032:analysis; D004195:Disease Models, Animal; D005289:Ferrets; D019084:Fluorescent Antibody Technique, Indirect; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D007106:Immune Sera / Q000276:immunology; D007165:Immunosuppression Therapy; D008168:Lung / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D011010:Pneumocystis / Q000235:genetics / Q000302:isolation & purification; D011020:Pneumonia, Pneumocystis / Q000276:immunology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley
D004271:DNA, Fungal; D007106:Immune Sera; D000244:Adenosine Diphosphate; D019204:GTP-Binding Proteins