PMID- 11129658
OWN - NLM
STAT- MEDLINE
DCOM- 20010111
LR  - 20181130
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 68
IP  - 6
DP  - 2000 Dec
TI  - Role of IL-12 in macrophage activation during intracellular infection: IL-12 and 
      mycobacteria synergistically release TNF-alpha and nitric oxide from macrophages 
      via IFN-gamma induction.
PG  - 897-902
AB  - IL-12 is believed to play an important role in cell-mediated immunity against 
      intracellular infection primarily by acting on T and NK cells. Recent evidence 
      has suggested, however, that IL-12 has broader cellular targets than previously 
      thought. In this study, we examined the role of IL-12 in macrophage TNF-alpha and 
      nitric oxide (NO) release by using an in vitro model of intracellular infection. 
      IL-12 alone released relatively little TNF-alpha and NO, whereas live 
      mycobacteria alone released TNF-alpha markedly but little NO from murine alveolar 
      macrophages. However, IL-12 and mycobacteria together enhanced TNF-alpha and NO 
      release synergistically. Because IL-12 and mycobacteria also released IFN-gamma 
      from macrophages synergistically, and exogenous IFN-gamma with mycobacteria 
      enhanced TNF-alpha and NO release synergistically, we examined the role of 
      endogenous IFN-gamma in IL-12/mycobacteria-stimulated macrophage activation. 
      Using macrophages from mice deficient in IFN-gamma, we found that 
      IL-12/mycobacteria-enhanced macrophage TNF-alpha and NO release was mediated 
      through endogenous IFN-gamma. We further demonstrated that IFN-gamma and 
      mycobacteria together had a selective effect on macrophage cytokine release 
      because they released TNF-alpha synergistically but not macrophage chemotactic 
      protein-1 (MCP-1). These findings reveal that IL-12 can activate macrophages 
      potently during intracellular infection, and this activating effect is mediated 
      primarily through its effect on macrophage IFN-gamma release.
FAU - Xing, Z
AU  - Xing Z
AD  - Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, 
      McMaster University, Hamilton, Ontario, Canada. xingz@fhs.mcmaster.ca
FAU - Zganiacz, A
AU  - Zganiacz A
FAU - Santosuosso, M
AU  - Santosuosso M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 187348-17-0 (Interleukin-12)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Interferon-gamma/biosynthesis/deficiency/genetics/pharmacology/*physiology
MH  - Interleukin-12/deficiency/genetics/pharmacology/*physiology
MH  - Macrophage Activation/*drug effects
MH  - Macrophages, Alveolar/metabolism/*microbiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mycobacterium bovis/*physiology
MH  - Nitric Oxide/*metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2000/12/29 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/12/29 11:00
PHST- 2000/12/29 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/12/29 11:00 [entrez]
PST - ppublish
SO  - J Leukoc Biol. 2000 Dec;68(6):897-902.