Pneumocystis carinii glycoprotein A inhibits surfactant phospholipid secretion by rat alveolar type II cells.
Pneumocystis carinii pneumonia (PCP) remains a major cause of morbidity in AIDS. The pathogenesis of PCP is poorly understood, but evidence of surfactant abnormalities is mounting. The role of the major surface glycoprotein of P. carinii, gpA, in producing surfactant abnormalities was investigated. Rat type II pneumocytes were incubated with [3H]choline, purified gpA, and modulators. Lipid was extracted, and [3H]dipalmitoyl phosphatidylcholine (DPPC) secretion was calculated. Contaminating endotoxin had no effect on DPPC secretion. gpA inhibited basal and ATP-stimulated DPPC secretion in a dose- and time-dependent manner. An anti-gpA monoclonal antibody attenuated inhibition of DPPC secretion. Unglycosylated recombinant gpA inhibited secretion, suggesting that functional activity resides in the protein moiety of gpA. These results suggest that gpA is a specific trigger for abnormalities of surfactant lipids in PCP. This is a unique role for a microbial product in disease pathogenesis and a potentially exploitable therapeutic target.
Lipschik
G Y
GY
Pulmonary Division, Allegheny University Hospitals-Medical College of Pennsylvania Division, Philadelphia, USA.
Treml
J F
JF
Moore
S D
SD
Beers
M F
MF
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D002478:Cells, Cultured / Q000378:metabolism; D004731:Endotoxins / Q000009:adverse effects; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008055:Lipids / Q000032:analysis / Q000302:isolation & purification; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D011010:Pneumocystis / Q000737:chemistry / Q000472:pathogenicity; D016720:Pneumocystis Infections / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D019138:Antibodies, Blocking; D004731:Endotoxins; D005656:Fungal Proteins; D008055:Lipids; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C077556:GPA protein, Pneumocystis carinii sp.; D015060:1,2-Dipalmitoylphosphatidylcholine; D000255:Adenosine Triphosphate