Pneumocystis carinii pneumonia alters expression and distribution of lung collectins SP-A and SP-D

Surfactant proteins SP-A and SP-D, members of the collectin family, have be en shown to play a significant role in lung host defense, Both proteins sel ectively bind Pneumocystis carinii (PC) organisms and modulate the interact ion of this pathogen with alveolar macrophages, We hypothesized that the ex pression and distribution of lung collectins SP-A and SP-D is altered by PC lung infection. PC organisms (2 x 10(5)) were inoculated intratracheally i nto C.B-17 scid/scid mice that do not require steroids for immunosuppressio n. Four weeks after inoculation, bronchoalveolar lavage (BAL) fluid was fra ctionated into three fractions-cell pellet, large aggregate (LA), and small aggregate (SA) surfactant-and each fraction was analyzed for the expressio n of surfactant components. In uninfected mice, the majority of SP-A (62% /- 10%) was found in association with lipids in the LA fraction, while 55% +/- 14% of SP-D was distributed in the SA fraction. In contrast, both hydro phobic proteins SP-B and SP-C were associated exclusively with LA, PC infec tion resulted in major changes in the expression of all surfactant componen ts. Total protein content of LA was unchanged by PC infection (115% +/- 18% of control), whereas SA protein content markedly increased (240% +/- 18% o f control level, P < .001), In contrast, the phospholipid content of LA was significantly decreased (53% +/- 5% of control level, P < .001), whereas t he SA phospholipid content of infected mice was increased (172% +/- 16% of control level, P < .001). By Western blotting, PC pneumonia (PCP) induced a 3-fold increase in the total alveolar SP-D protein that was reflected main ly in increases in SA SP-D (454% +/- 135% of control, P < .05). The total a lveolar SP-A protein content was also increased in PCP because of a large i ncrease in SP-A in SA (720% +/- 115% of control, P < .05); SP-A levels in L A were unchanged. The increases in lung collectin expression were selective , because PCP resulted in the down-regulation of both SP-B and SP-C in LA ( 5% +/- 2% and 13% +/- 2% of control, respectively, P < .001). We conclude t hat PCP induces marked elevations in alveolar collectin levels because of i ncreased expression and accumulation of SP-A and SP-D protein in SA surfact ant.