Roles of calcium and annexins in phagocytosis and elimination of an attenuated strain ofMycobacterium tuberculosisin human neutrophils |
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| Institution: | 1. Department of Medical Microbiology, Linköping University, Linköping, S-581 85, Sweden;2. Division of Infectious Diseases and Rosalind Russell Research Laboratory, University of California, San Francisco and San Francisco General Hospital, San Francisco, CA, U.S.A.;1. Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil;2. Department of Chemistry, Federal University of Pernambuco, Pernambuco, Recife, Brazil;1. Siberian State Medical University, Tomsk, Russia;2. Cardiovascular Division, Department of Medicine, Vanderbilt University, Nashville, TN, USA;3. Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA;1. Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA;2. Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA;3. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA;4. Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA;5. Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA;6. Department of Human Pathology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia;7. Nanosafety & Nanomedicine Laboratory, Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden |
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| Abstract: | The phagocytic function of neutrophils is a crucial element in the host defence against invading microorganisms. We investigated phagocytosis and intracellular killing of an attenuated strain ofMycobacterium tuberculosis(H37Ra) by human neutrophils focusing on the role of the cytosolic free calcium concentration Ca2+]iand certain cytosolic calcium-dependent membrane-binding proteins annexins. Phagocytic uptake did not trigger a calcium rise and occurred independently of different calcium conditions, and in a serum-dependent manner. Changes in the viability of H37Ra were determined by agar plate colony count and a radiometric assay. Neutrophils showed a capacity to kill ingested mycobacteria and this occurred without a rise in Ca2+]i. The ability to kill H37Ra decreased in the absence of extracellular calcium and when intra-extracellular calcium was reduced. Immunofluorescence staining revealed that during phagocytosis of H37Ra, annexins III, IV and VI translocated from cytoplasm to the proximity of the H37Ra-containing phagosomes, whereas the localization of annexin I and V remained unchanged. The translocation of annexin IV occurred even when Ca2+-depleted neutrophils ingested H37Ra in the absence of extracellular calcium. We concluded that neutrophil-mediated killing of mycobacteria is a Ca2+-dependent process. The fact that the association of certain annexins to the membrane vesicle containing H37Ra differ from other phagosomes suggests a selective regulatory mechanism during phagocytosis of mycobacteria by neutrophils. |
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