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Macrophage Activation

Macrophage Activation

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Macrophage Activation
Pro-inflammatory effects:
  • Stimulation by specific cytokines, such as interferon gamma (aka, type II interferon) and/or by microbes activate macrophages to produce inducible nitric oxide, reactive oxygen species, and lysosomal enzymes, which are antimicrobial.
  • These activated macrophages also produce inflammatory cytokines and chemokines:
– Tumor necrosis factor and chemokines activate lymphocytes.
  • Activated T lymphocytes produce interferon gamma, which, as we've indicated, triggers pro-inflammatory macrophage activation. Thus, T lymphocytes can act as part of a positive feedback loop with pro-inflammatory activated macrophages.
Anti-inflammatory effects:
  • Anti-inflammatory stimuli include interleukins 13 and 4 (IL-13, IL-4).
– In response to these stimuli, activated macrophages produce cytokines, such as interleukin-10 (IL-10), that inhibit inflammatory activity of T lymphocytes, natural killer cells, and macrophages; thus, interleukin 10 prevents excessive inflammation and damage to host cells. – These "alternatively activated" macrophages also produce growth factors that promote tissue repair, including vascular endothelial growth factor (VEGF), which facilitates angiogenesis, and transforming growth factor beta (TGF-ß), which facilitates deposition of extracellular matrix proteins for fibrosis.
  • Interleukins 13 and 4 (IL-13 and IL-4) are produced by T lymphocytes; thus, T lymphocytes can also promote anti-inflammatory macrophage activation.
Be aware that some texts describe two distinct types of macrophage activation, classical and alternative, and the resulting macrophages as either Type 1 (aka, classical type) or Type 2 (aka, alternative type); however, research now suggests that these should not be thought of as dichotomous types, but, rather, as potential phenotypes that macrophages express in response to environmental stimuli.
  • Upon activation, macrophages engage in various activities:
– Presentation of antigens to T lymphocytes. – Production of cytokines, which mediate inflammatory responses. – Production of growth factors and enzymes that promote tissue repair and inhibit inflammation.
  • To accomplish these goals, macrophages have dynamic phenotypes reflective of their microenvironments.

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