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Infection and Immunity, February 2001, p. 758-764, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.758-764.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Pulmonary Inflammation Disrupts Surfactant Function during Pneumocystis carinii Pneumonia

Terry W. Wright,1,* Robert H. Notter,1 Zhengdong Wang,1 Allen G. Harmsen,2 and Francis Gigliotti1

Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642,1 and Trudeau Institute, Saranac Lake, New York 129832

Received 26 April 2000/Returned for modification 23 June 2000/Accepted 7 November 2000

During Pneumocystis carinii pneumonia (PCP) in mice, the degree of pulmonary inflammation correlates directly with the severity of lung function deficits. Therefore, studies were undertaken to determine whether the host inflammatory response contributes to PCP-related respiratory impairment, at least in part, by disrupting the pulmonary surfactant system. Protein and phospholipid content and surfactant activity were measured in the lavage fluid of infected mice in either the absence or presence of an inflammatory response. At 9 weeks postinfection with P. carinii, nonreconstituted SCID mice exhibited no signs of pulmonary inflammation, respiratory impairment, or surfactant dysfunction. Lavage fluid obtained from these mice had protein/phospholipid (Pr/PL) ratios (64% ± 4.7%) and minimum surface tension values (4.0 ± 0.9 mN/m) similar to those of P. carinii-free control mice. However, when infected SCID mice were immunologically reconstituted, an intense inflammatory response ensued. Pr/PL ratios (218% ± 42%) and minimum surface tension values (27.2 ± 2.7 mN/m) of the lavage fluid were significantly elevated compared to those of the lavage fluid from infected, nonreconstituted mice (P < 0.05). To examine the specific role of CD8+ T-cell-mediated inflammation in surfactant dysfunction during PCP, mice with defined T-cell populations were studied. P. carinii-infected, CD4+-depleted mice had elevated lavage fluid Pr/PL ratios (126% ± 20%) and elevated minimum surface tension values (16.3 ± 1.0 mN/m) compared to normal mice (P < 0.05). However, when infected mice were additionally depleted of CD8+ cells, Pr/PL ratios were normal and surfactant activity was improved. These findings demonstrate that the surfactant pathology associated with PCP is related to the inflammatory process rather than being a direct effect of P. carinii. Moreover, CD8+ lymphocytes are involved in the mechanism leading to surfactant dysfunction.

* Corresponding author. Mailing address: Department of Pediatrics, P.O. Box 690, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester, NY 14642. Phone: (716) 275-5944. Fax: (716) 273-1104. E-mail: Terry_Wright{at}urmc.rochester.edu.

Infection and Immunity, February 2001, p. 758-764, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.758-764.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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