Direct stimulation of macrophages by IL-12 and IL-18--a bridge too far?
A novel pathway of autocrine macrophage activation based on a positive feedback loop involving interleukin (IL)-12, IL-18 and IFN-gamma has recently been suggested. However, the macrophage isolation technique employed to describe the above phenomenon does not allow obtaining a pure population of macrophages casting some doubt to its existence. In the present study, we show that even minor contamination with lymphoid cells of a pure population of macrophage-like cells (Raw 264.7) results in a marked production of nitric oxide after stimulation with both IL-12 and IL-18. Neither macrophage-like cells nor lymphoid cells were capable of secreting high amounts of nitric oxide after stimulation with IL-12 and/or IL-18. Based on these observations we hypothesize that proposed autocrine feedback loop of macrophage activation is rather paracrine in nature and involves direct stimulation of residual lymphoid cells to secrete IFN-gamma that is then capable of activating macrophages.
Gołab
J
J
Department of Immunology, Institute of Biostructure, The Medical University of Warsaw, ul. Chalubińskiego 5, 02-004, Warsaw, Poland. jgolab@ib.amwaw.edu.pl
Zagozdzon
Stokłosal
T
T
Kamiński
R
R
Kozar
K
K
Jakóbisiak
M
M
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000276:immunology* / Q000494:pharmacology; D020382:Interleukin-18 / Q000276:immunology* / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009569:Nitric Oxide / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology
D020382:Interleukin-18; D011994:Recombinant Proteins; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma