P. carinii induces selective alterations in component expression and biophysical activity of lung surfactant

Studies of Pneumocystis carinii pneumonia (PCP) suggest an important role f or the surfactant system in the pathogenesis of the hypoxemic respiratory i nsufficiency associated with this infection. We hypothesized that PCP induc es selective alterations in alveolar surfactant component expression and re sultant biophysical properties. PCP was induced by intratracheal inoculatio n of 2 x 10(5) P carinii organisms into C.B-17 scid/scid mice. Six weeks af ter inoculation, large (LA)- and small (SA)-aggregate surfactant fractions were prepared from bronchoalveolar lavage fluids and analyzed for expressio n of surfactant components and for biophysical activity. Total phospholipid content was significantly reduced in LA surfactant fractions from mice inf ected with PCP (53 +/- 15% of uninfected mice; P < 0.05). Quantitation of h ydrophobic surfactant protein (SP) content demonstrated significant reducti ons of alveolar SP-B and SP-C protein levels in mice with PCP compared with those in uninfected mice (46 +/- 7 and 19 +/- 6%, respectively; P < 0.05 f or both). The reductions in phospholipid, SP-B, and SP-C in LA fractions me asured during PCP were associated with an increase in the minimum surface t ension of LAs as measured by pulsating bubble surfactometer 13.1 +/-: 1.1 v s, 5.4 +/- 1.8 mN/m; P < 0.05. In contrast to decreases in the hydrophobic SPs, SP-D content in the SA fraction was markedly increased (343 +/- 30% of control value; P < 0.05) and SP-A levels in LA surfactant were maintained (93 +/- 26% of control value) during P. carinii infection. In all cases, th e changes in SP content were reflected by commensurate changes in the level s of mRNA. We conclude that PCP induces selective alterations in surfactant component expression,: including-profound decreases in hydrophobic protein contents and resultant increases in surface tension. These changes, demons trated in an immunologically relevant animal model, suggest that alteration s in surfactant could contribute to the hypoxemic respiratory insufficiency observed in PCP.