Cytosolic phospholipase A2 enzymes are not required by mouse bone marrow-derived macrophages for the control of Mycobacterium tuberculosis in vitro.
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.
Vandal
Omar H
OH
Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Box 57, New York, NY 10021, USA.
Gelb
Michael H
MH
Ehrt
Sabine
S
Nathan
Carl F
CF
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D054467:Phospholipases A2
D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2