Inhibition of surfactant activity by Pneumocystis carinii organisms and components in vitro.
This study examines the direct inhibitory effects of Pneumocystis carinii (Pc) organisms and chemical components on the surface activity and composition of whole calf lung surfactant (WLS) and calf lung surfactant extract (CLSE) in vitro. Incubation of WLS suspensions with intact Pc organisms (10(7) per milligram of surfactant phospholipid) did not significantly alter total phospholipid levels or surfactant protein A content. Incubation with intact Pc organisms also did not impair dynamic surface tension lowering in suspensions of WLS or centrifuged large surfactant aggregates on a bubble surfactometer (37 degrees C, 20 cycles/min, 0.5 and 2.5 mg phospholipid/ml). However, exposure of WLS or CLSE to disrupted (sonicated) Pc organisms led to severe detriments in activity, with minimum surface tensions of 17-19 mN/m vs. <1 mN/m for surfactants alone. Extracted hydrophobic chemical components from Pc (98.8% lipids, 0.1 mM) reduced the surface activity of WLS and CLSE similarly to sonicated Pc organisms, whereas extracted hydrophilic chemical components from Pc (primarily proteins) had only minor effects on surface tension lowering. These results indicate that in addition to surfactant dysfunction induced by inflammatory lung injury and edema-derived inhibitors in Pc pneumonia, disrupted Pc organisms in the alveolar lumen also have the potential to directly inhibit endogenous and exogenous lung surfactants in affected patients.
Wang
Zhengdong
Z
Dept. of Pediatrics, Box 850, Univ. of Rochester School of Medicine, 601 Elmwood Ave., Rochester, NY 14642, USA.
Foye
Adam
A
Chang
Yusuo
Y
Chess
Patricia R
PR
Wright
Terry W
TW
Bhagwat
Samir
S
Gigliotti
Francis
F
Notter
Robert H
RH
D000818:Animals; D002417:Cattle; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D010743:Phospholipids / Q000378:metabolism*; D045363:Pneumocystis carinii / Q000472:pathogenicity*; D011020:Pneumonia, Pneumocystis / Q000276:immunology / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D013500:Surface Tension
D010743:Phospholipids; D037662:Pulmonary Surfactant-Associated Protein A; D011663:Pulmonary Surfactants