120-kD surface glycoprotein of Pneumocystis carinii is a ligand for surfactant protein A.

Abstract

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.

Surfactant protein-A levels increase during Pneumocystis carinii pneumonia in the rat

“…A number of recent in vitro studies have suggested that SP-A might be involved in pulmonary host-defence, and in phagocytosis in particular [11][12][13][14][15][16][17][18], and an interaction between SP-A and P. carinii has been demonstrated [20]. Preliminary studies suggest that although SP-A may stimulate the in vitro phagocytosis of some organisms [10,11,15], such as Candida albicans, Staphylococcus aureus and Herpes simplex, it may interfere with the phagocytosis of P. carinii by alveolar macrophages [10].…”

“…A number of striking similarities have been noted between SP-A and proteins involved in host defence in the alveolar lining layer. Interaction between SP-A and P. carinii has been demonstrated [20], and studies by our group suggest that this interaction interferes with the phagocytosis of P. carinii by alveolar macrophages ([10] -manuscript submitted). In the present study, we examined the production of SP-A messenger ribonucleic acid (mRNA) and protein in rats over time, in the presence and absence both of glucocorticoid-induced immunosuppression and infection with P. carinii.…”

Collectins — soluble proteins containing collagenous regions and lectin domains — and their roles in innate immunity

“…However, in addition to these properties, SP-A also has been shown to enhance the phagocytosis of bacteria and viruses by alveolar macrophages (Van Iwarden et al, 1991) and to induce the production of oxygen radicals by these cells. The binding of SP-A, via its lectin domain, has been shown to take place with the gp120 glycoprotein of Pneumocystis carinii (Zimmerman et al, 1992) and with Staphylococcus aureus (McNeely & Coon-rod, 1993), the latter binding enhancing the adherence of the SP-A coated bacteria to alveolar macrophages. SP-D is present at an approximately IO-fold lower level in the lung than SP-A, as judged by analysis of bronchoalveolar iavage.…”

Affinity and kinetic analysis of the bovine plasma C‐type lectin collectin‐43 (CL‐43) interacting with mannan

“…The collectins have been shown to bind to the surface of various micro-organisms and particles, and the critical discriminatory event in this process is the interaction of the Ctype lectin domain of the collectins and microbial carbohydrates [4][5][6][7][8][9]. One collectin, MBL, can enhance opsonization by activation of the classical pathway of complement in a Clq-and antibody-independent way [10][11][12][13].…”