Cytosolic phospholipase A2 enzymes are not required by mouse bone marrow-derived macrophages for the control of Mycobacterium tuberculosis in vitro.

TitleCytosolic phospholipase A2 enzymes are not required by mouse bone marrow-derived macrophages for the control of Mycobacterium tuberculosis in vitro.
Publication TypeJournal Article
Year of Publication2006
AuthorsVandal OH, Gelb MH, Ehrt S, Nathan CF
JournalInfect Immun
Volume74
Issue3
Pagination1751-6
Date Published2006 Mar
ISSN0019-9567
KeywordsAnimals, Arachidonic Acid, Cytosol, Macrophages, Mice, Mycobacterium tuberculosis, Phospholipases A, Phospholipases A2
Abstract

During the course of infection Mycobacterium tuberculosis predominantly resides within macrophages, where it encounters and is often able to resist the antibacterial mechanisms of the host. In this study, we assessed the role of macrophage phospholipases A2 (PLA2s) in defense against M. tuberculosis. Mouse bone marrow-derived macrophages (BMDMs) expressed cPLA2-IVA, cPLA2-IVB, iPLA2-VI, sPLA2-IIE, and sPLA2-XIIA. The expression of cPLA2-IVA was increased in response to M. tuberculosis, gamma interferon, or their combination, and cPLA2-IVA mediated the release of arachidonic acid, which was stimulated by M. tuberculosis in activated, but not unactivated, macrophages. We confirmed that arachidonic acid is highly mycobactericidal in a concentration- and pH-dependent manner in vitro. However, when M. tuberculosis-infected macrophages were treated with PLA2 inhibitors, intracellular survival of M. tuberculosis was not affected, even in inducible nitric oxide synthase-deficient macrophages, in which a major bactericidal mechanism is removed. Moreover, intracellular survival of M. tuberculosis was similar in cPLA2-IVA-deficient and wild-type macrophages. Our results demonstrate that the cytosolic PLA2s are not required by murine BMDMs to kill M. tuberculosis.

DOI10.1128/IAI.74.3.1751-1756.2006
Alternate JournalInfect Immun
PubMed ID16495548
PubMed Central IDPMC1418652
Grant ListR01 HL072718 / HL / NHLBI NIH HHS / United States
HL72718 / HL / NHLBI NIH HHS / United States

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