Role of leukotrienes in killing of Mycobacterium bovis by neutrophils.
The neutrophil (PMN) plays an important role in the phagocytosis and killing of microorganisms. Pro-inflammatory leukotrienes (LT) play an important role in various disease states. However LT elaborated by PMN have also been shown to be important in host defense, specifically phagocytosis and killing of microorganisms. Defective LT synthesis by phagocytes correlates with their reduced anti-microbial activity. Therefore, we determined if LT played an important role in the killing of Mycobacteria bovis (M. bovis) by PMN. Endogenous LT play a role in the killing of mycobacteria since the LT synthesis inhibitor MK-886 reversed the killing of M. bovis by PMN. Increased synthesis of LT occurred following incubation of PMN with M. bovis. Treatment with granulocyte-colony stimulating factor, which augments PMN LT synthesis, also boosted anti-microbial activity. Furthermore, exogenous LTB4 augmented dose-dependent killing of M. bovis by PMN. In conclusion, LT play a vital role in promoting mycobactericidal actions of PMN.
Coffey
Michael Joseph
MJ
Division of Pulmonary Medicine, Department of Internal Medicine, University of Michigan Health System, 6301 MSRB III, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-0642, USA. coffeym@umich.edu
Phare
Susan M
SM
Peters-Golden
Marc
M
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000494:pharmacology; D015289:Leukotrienes / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009163:Mycobacterium bovis; D009504:Neutrophils / Q000378:metabolism* / Q000382:microbiology; D002722:Chlorobenzenes
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007211:Indoles; D007975:Leukotriene B4; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; C060893:MK-886; D002722:Chlorobenzenes