Human monocyte differentiation stage affects response to arachidonic acid.
AA-induced cell death mechanisms acting on human monocytes and monocyte-derived macrophages (MDM), U937 promonocytes and PMA-differentiated U937 cells were studied. Arachidonic acid induced apoptosis and necrosis in monocytes and U937 cells but only apoptosis in MDM and U937D cells. AA increased both types of death in Mycobacterium tuberculosis-infected cells and increased the percentage of TNFalpha+ cells and reduced IL-10+ cells. Experiments blocking these cytokines indicated that AA-mediated death was TNFalpha- and IL-10-independent. The differences in AA-mediated cell death could be explained by high ROS, calpain and sPLA-2 production and activity in monocytes. Blocking sPLA-2 in monocytes and treatment with antioxidants favored M. tuberculosis control whereas AA enhanced M. tuberculosis growth in MDM. Such evidence suggested that AA-modulated effector mechanisms depend on mononuclear phagocytes' differentiation stage.
Grupo de Inmunología Celular e Inmunogenética, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Elizabeth
E
Escobar-Alvarez
Carlos A
CA
Pelaez
Luis F
LF
García
Mauricio
M
Rojas
D019138:Antibodies, Blocking; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016718:Arachidonic Acid / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D009336:Necrosis; D010711:Phosphatidate Phosphatase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D014376:Tuberculosis / Q000097:blood / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D020298:U937 Cells
D019138:Antibodies, Blocking; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016718:Arachidonic Acid; C406242:phosphatidic acid phosphatase type 2; D010711:Phosphatidate Phosphatase; D002154:Calpain