Journal article
Pulmonary surfactant protein A mediates enhanced phagocytosis of Mycobacterium tuberculosis by a direct interaction with human macrophages
The Journal of immunology (1950), Vol.155(11), pp.5343-5351
12/01/1995
DOI: 10.4049/jimmunol.155.11.5343
PMID: 7594549
Abstract
During initial infection with Mycobacterium tuberculosis, bacteria that reach the distal airspaces of the lung are phagocytosed by alveolar macrophages in the presence of pulmonary surfactant. Here we have examined the role of surfactant-associated protein A (SP-A) in phagocytosis of the virulent Erdman strain of M. tuberculosis by human monocyte-derived macrophages (MDMs) and human alveolar macrophages (HAMs). Macrophage monolayers incubated with soluble SP-A from alveolar proteinosis patients (APP SP-A4) and recombinant rat SP-A (SP-Ahyp) demonstrated enhanced adherence of M. tuberculosis, 82 +/- 17% and 49 +/- 18%, respectively. Removal of SP-A from monolayers by washing before adding bacteria did not diminish the enhanced adherence. Fluorescence microscopy demonstrated that washed monolayers contained intracellular rather than surface-bound SP-A. These studies indicated a direct interaction between SP-A and the macrophage in mediating enhanced adherence of M. tuberculosis. Consistent with this interpretation, macrophage monolayers formed on human or rat SP-A (substrate SP-A) demonstrated enhanced adherence of M. tuberculosis to their apical surface (APP SP-A and native rat SP-A increased M. tuberculosis adherence by 102 +/- 16% and 102 +/- 25%, respectively). Electron microscopy demonstrated increased numbers of phagocytosed bacteria in APP SP-A-treated MDM cross-sections. SP-A proteins devoid of carbohydrate failed to enhance M. tuberculosis adherence to macrophages. In contrast, heat-denatured APP SP-A enhanced adherence of bacteria equivalent to that of intact glycoprotein. Thus, the carbohydrate moieties of SP-A appear to be critical in the SP-A-macrophage interaction. Finally, mannan and anti-mannose receptor Ab completely inhibited the enhanced phagocytosis of M. tuberculosis observed with APP SP-A, providing evidence for up-regulation of macrophage mannose receptor activity. These studies implicate SP-A as an important modulator of alveolar macrophage function that results in an enhanced potential for M. tuberculosis to gain access to its intracellular niche.
Details
- Title: Subtitle
- Pulmonary surfactant protein A mediates enhanced phagocytosis of Mycobacterium tuberculosis by a direct interaction with human macrophages
- Creators
- Celia D Gaynor - Department of Medicine, Department of Veterans Affairs, Iowa City, IA, USAFrancis X McCormackDennis R VoelkerStephen E McGowanLarry S Schlesinger
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.155(11), pp.5343-5351
- Publisher
- United States
- DOI
- 10.4049/jimmunol.155.11.5343
- PMID
- 7594549
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- AI33004 / NIAID NIH HHS HL51990 / NHLBI NIH HHS HL45286 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/01/1995
- Academic Unit
- International Programs; Internal Medicine
- Record Identifier
- 9983984539702771
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