Macrophage-independent Fungicidal Action of the Pulmonary Collectins
| Autor: | Reta S. Gibbons, Alexander Kuzmenko, George S. Deepe, Susan R. Ward, Huixing Wu, Francis X. McCormack |
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| Rok vydání: | 2003 |
| Předmět: |
Time Factors
Transgene Histoplasma Collectin Mice Transgenic Biology Biochemistry Microbiology Rats Sprague-Dawley Mice Leukocytes medicine Animals Humans Lung Molecular Biology Alleles Mice Inbred C3H Dose-Response Relationship Drug Pulmonary Surfactant-Associated Protein A Macrophages Stem Cells Intracellular parasite Cell Biology Alkaline Phosphatase Flow Cytometry Pulmonary Surfactant-Associated Protein D Collectins Recombinant Proteins Yeast Rats Agar Dose–response relationship medicine.anatomical_structure Alkaline phosphatase Cell Division Spleen Intracellular |
| Zdroj: | Journal of Biological Chemistry. 278:36250-36256 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m303086200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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