Pneumocystis carinii is the most common cause oflife-threatening pneumonia in immunocompromised patients. In the current study, surfactant protein A (SP-A), the major nonserum protein constituent of pulmonary surfactant, is demonstrated to bind P. carinii in a specific and saturable manner. SP-A is surface bound and does not appear to be internalized or degraded by the P. carini organism. Furthermore, SP-A binding to P. carini' is time-and calcium-dependent and is competitively inhibited by mannosyl albumin. In the absence of calcium or the presence of excess mannosyl albumin, SP-A binding to P. carinii is reduced by 95 and 71%, respectively. SP-A avidly binds P. carinil with a Kd of8 x 10-9 M and an estimated 8.4 X 106 SP-A binding sites per P. carinii organism, as determined from Scatchard plots. SP-A is shown to bind P. carinli in vivo, and a putative binding site for SP-A on P. carini is demonstrated to be the mannoserich surface membrane glycoprotein gpl20. These findings suggest that P. carinii can interact with the phospholipid-rich material in the alveolar spaces by specifically binding a major protein constituent of pulmonary surfactant. (J. Clin. Invest.

The purpose of this study was to determine if the measurement of surfactant protein A (SP-A) in bronchoalveolar lavage (BAL) fluid predicts survival in patients with idiopathic pulmonary fibrosis (IPF). We performed BAL on 44 patients with IPF and 33 healthy volunteers. SP-A and total phospholipid (PL) were measured in the surfactant pelleted by centrifugation and expressed as a ratio to account for differences in the alveolar surface area sampled. The mean SP-A/PL was lower in patients with IPF than in healthy volunteers (31.8 +/- 2.8 versus 63.9 +/- 6.4 micrograms/mumol, p = 0.006) and in patients who died within 2 yr than in those who survived (23.4 +/- 2.6 versus 37.5 +/- 4.2 micrograms/mumol, p = 0.015). Using Cox's proportional hazard model, we found that SP-A/PL modeled continuously was associated with survival time (p = 0.002). The 5-yr survival of patients with SP-A/PL above the median level for all patients with IPF (29.7 micrograms/mumol) was more than twice that of patients below the median (68 versus 30%, p = 0.007). SP-A/PL improved upon prediction of survival modeled by most routine physiologic variables with the exception of percent predicted TLC or the multifarious clinical-radiographic-physiologic score (CRP). Cellular analysis of lavage did not predict survival in this cohort of patients. We conclude that SP-A/PL is a biochemical marker in lavage that predicts survival in patients with IPF.

Alveolar macrophage and type II cells are known to generate nitric oxide, which is a highly reactive molecule that plays a role in host defense against pathogens, as well as tissue damage associated with inflammation in the lung. Both types of cells are known to generate the nitric oxide by inducible nitric oxide synthase (iNOS). Surfactant-associated protein A (SP-A) from various sources (human alveolar proteinosis, rat and recombinant rat) was found to upregulate nitric oxide production by alveolar macrophages in a concentration- and time-dependent manner, whereas type II cells were unresponsive to SP-A. The increase in nitric oxide production was associated with elevation in the expression of iNOS. However, only 30-50% of the cells responded by expressing iNOS, as was observed by immunofluorescence staining. The stimulatory effect of SP-A was found to be 30-50% lower than the known nitric oxide agonists interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). However, addition of the cytokines interleukin-1 or granulocyte macrophage colony-stimulating factor elevated the levels of nitric oxide production to that of LPS and IFN-gamma. Special attention was given to exclude the possibility that contaminating LPS in the various SP-A species stimulated nitric oxide production by the macrophages. Our results indicate that SP-A is the agonist and not a contaminating LPS. The data presented in this report extend our knowledge regarding the nonsurfactant-related functions of SP-A.

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