Pulmonary inflammation disrupts surfactant function during Pneumocystis carinii pneumonia

During Pneumocystis carinii pneumonia (PCP) in mice, the degree of pulmonar y inflammation correlates directly with the severity of lung function defic its. Therefore, studies were undertaken to determine whether the host infla mmatory response contributes to PCP-related respiratory impairment, at leas t in part, by disrupting the pulmonary surfactant system, Protein and phosp holipid content and surfactant activity were measured in the lavage fluid o f infected mice in either the absence or presence of an inflammatory respon se, At 9 weeks postinfection with P. carinii, nonreconstituted SCID mice ex hibited no signs of pulmonary inflammation, respiratory impairment, or surf actant dysfunction, Lavage fluid obtained from these mice had protein/phosp holipid (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 inf lammatory response ensued, Pr/PL ratios (218% +/- 42%) and minimum surface tension values (27.2 +/- 2.7 mN/m) of the lavage fluid were significantly e levated compared to those of the lavage fluid from infected, nonreconstitut ed 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 el evated lavage fluid Pr/PL ratios (126% +/- 20%) and elevated minimum surfac e tension values (16.3 +/- 1.0 mN/m) compared to normal mice (P < 0.05). Ho wever, when infected mire were additionally depleted of CD8(+) cells, Pr/PL ratios were normal and surfactant activity was improved, These findings de monstrate that the surfactant pathology associated with PCP is related to t he inflammatory process rather than being a direct effect of P. carinii. Mo reover, CD8(+) lymphocytes are involved in the mechanism leading to surfact ant dysfunction.