| First Author | McCormack FX | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 38 | Pages | 36250-6 |
| PubMed ID | 12857753 | Mgi Jnum | J:85539 |
| Mgi Id | MGI:2675574 | Doi | 10.1074/jbc.M303086200 |
| Citation | McCormack FX, et al. (2003) Macrophage-independent fungicidal action of the pulmonary collectins. J Biol Chem 278(38):36250-6 |
| abstractText | Histoplasma capsulatum (Hc) is a facultative intracellular fungal pathogen that causes acute and chronic pneumonia. In this study, we investigated the role of the pulmonary collectins, surfactant proteins (SP) A and D, in the clearance of Hc yeast from the lung. Exposure of yeast to either collectin induced a dose-dependent decrease in [3H]leucine incorporation by several strains of Hc. This decrement was attributed to killing of the collectin-exposed yeast since it failed to grow on agar medium. Exposure to SP-A or -D resulted in increased yeast permeability based on a leak of protein from the organism and enhanced access of an impermeant substrate to intracellular alkaline phosphatase. Inbred and outbred SP-A null (-/-) mice were modestly more susceptible to pulmonary infection with Hc than strain and age-matched SP-A (+/+) control mice. The increase in susceptibility was associated with a decrement in the number of CD8+ cells in the lungs of SP-A-/- mice. Neither SP-A nor SP-D inhibited the growth of macrophage-internalized Hc. We conclude that the SP-A and SP-D are antimicrobial proteins that directly inhibit the growth of Hc by increasing permeability of the organism and that Hc gains asylum from collectin-mediated killing by rapid entry into pulmonary macrophages. |
