120-kD surface glycoprotein of Pneumocystis carinii is a ligand for surfactant protein A.
Pneumocystis carinii is the most common cause of life-threatening pneumonia in immunocompromised patients. In the current study, surfactant protein A (SP-A), the major nonserum protein constituent of pulmonary surfactant, is demonstrated to bind P. carinii in a specific and saturable manner. SP-A is surface bound and does not appear to be internalized or degraded by the P. carinii organism. Furthermore, SP-A binding to P. carinii is time- and calcium-dependent and is competitively inhibited by mannosyl albumin. In the absence of calcium or the presence of excess mannosyl albumin, SP-A binding to P. carinii is reduced by 95 and 71%, respectively. SP-A avidly binds P. carinii with a Kd of 8 x 10(-9) M and an estimated 8.4 x 10(6) SP-A binding sites per P. carinii organism, as determined from Scatchard plots. SP-A is shown to bind P. carinii in vivo, and a putative binding site for SP-A on P. carinii is demonstrated to be the mannoserich surface membrane glycoprotein gp120. These findings suggest that P. carinii can interact with the phospholipid-rich material in the alveolar spaces by specifically binding a major protein constituent of pulmonary surfactant.
Zimmerman
P E
PE
Department of Internal Medicine, Indiana University School of Medicine, Indianapolis 46202.
Voelker
D R
DR
McCormack
F X
FX
Paulsrud
J R
JR
Martin
W J
WJ
D000818:Animals; D001665:Binding Sites; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008766:Methylmannosides / Q000378:metabolism; D011010:Pneumocystis / Q000737:chemistry*; D011020:Pneumonia, Pneumocystis / Q000378:metabolism*; D011510:Proteolipids / Q000276:immunology / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D012709:Serum Albumin; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms
D005656:Fungal Proteins; D008562:Membrane Glycoproteins; D008766:Methylmannosides; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012709:Serum Albumin; C023840:mannose-bovine serum albumin conjugate; D012710:Serum Albumin, Bovine; C008466:methylmannoside; D008358:Mannose; D002118:Calcium