Regulation of macrophage activation.
IFN-gamma rapidly primes the macrophage via JAK1/2-STAT1 pathway so that it can subsequently undergo a slower classical type 1 activation upon exposure to T helper (Th)1 cytokines such as IFNgamma or other activators, including tumor necrosis factor and lipopolysaccharide, e.g. in intracellular killing of phagocytosed Mycobacterium tuberculosis. If instead it is driven by Th2 cytokines interleukin (IL)-4 and IL-13, it undergoes alternate type 2 activation, which enhances endocytotic antigen uptake and presentation, mast cell and eosinophil involvement and type 2 granuloma formation, e.g. in response to parasitic and extracellular pathogens. Particle-induced macrophage activation was shown to differ from classical and alternate activation, showing in DNA microarray experiments (complete linkage/ Euclidean distance metric analysis) upregulation of nonsecreted structural/signaling molecules and lack of secreted proinflammatory cyto- and chemokines. The switch-off (deactivation) of already activated macrophages is an active, controlled process in which IL-10 and corticosteroids play important roles and to which 15dPGJ2, PGA1/2 and vasoactive intestinal peptide often contribute.
Ma
J
J
Department of Anatomy, Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
Chen
T
T
Mandelin
J
J
Ceponis
A
A
Miller
N E
NE
Hukkanen
M
M
Ma
G F
GF
Konttinen
Y T
YT
D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000502:physiology; D005547:Foreign Bodies / Q000276:immunology; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011956:Receptors, Cell Surface / Q000502:physiology; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology; D051193:Toll-Like Receptors
D016207:Cytokines; D006728:Hormones; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors