Question

how does macrophage activity relate to complement pathway. Give specific examples.

Answer 1

Macrophages are an important component of the innate immune system, they are characterized by the expression of number of unique surface markers including CD14, CD11b, CD11c, F4/80, MAC-1/MAC-3, CD163, and CD68 42, It has been found in number of tumor models that macrophages support cancer cells proliferation and survival.. Macrophage release TNF-α and activate NF-kB, which turns-on proteins that stop apoptosis, and promote cell proliferation . Macrophages maintain essentials of tissue remodeling, inflammation, and immunity, include endocytosis of foreign and necrotic debris, cytotoxicity, and secretion of more than different cytokines . However, depending on their activation, macrophages are able to secrete growth factors, prostaglandins, interferon, elastase, plasminogen activator, and collagenase, and complement components C3 and C5 Macrophages have classically activated M1 and alternatively activated M2 subtypes, and the differentiation in to respective subtype is mediated through the release of cytokines and growth factors present in the inflammatory microenvironment]. The development of M1 macrophages stimulated through IFN-γ and TNF-α.whereas, the M2 macrophages are polarized by IL-4, IL-13 As mentioned, the immunological effects of both M1 and M2 subtypes are regulated through the myriad of cytokines. It has been reported that IFN-γ stimulated M1 macrophages elevate the production of IL-12 and IL-23, and low IL-10 . However, M2 macrophages favor over production of IL-10 and low levels of IL-12 and IL-23. M1 macrophage secreted IL-12 promotes the differentiation of Th1 cells, which can improve antigen phagocytosis while IL-23 triggers the Th17 cells proliferation and release of IL-17, which modulates inflammatory autoimmune pathologies .On the other side, the M2 macrophage secreted IL-10 favor the production of IL-4 and IL-13 by Th2 cells. The M1 macrophage derived chemokines are also critical for killing intercellular pathogens, whereas the M2 macrophage derived chemokines promote the recruitment of the leukocytes involved in tissue repair and remodeling process It has been reported that macrophage polarization occurs during onset of tumor progression and it changes from classically activated M1 to alternatively activated M2 like Tumor-Associated Macrophages (TAMs) ]. Depending on the physiological and pathological conditions, macrophages undergo differentiation into M1 and M2 phenotypes and both play a key role in maintaining tumor growth . M1 macrophages are pro-inflammatory in function, they secrete IFN-γ, IL-12 and TNF-α, and therefore effectively suppress tumor growth while M2 like TAMs secrete TGF-β, IL-10, IL-17, IL-23, VEGF, and FGF2, promote angiogenesis and tumor progression (Fig. 3). M2 TAMs produce VEGF, FGF chemokines IL-17, IL-23, or TGF-β that contribute to stimulation of vascular endothelial cell proliferation, release of MMPs, which degrade the vascular basement membrane and induce sprouting, migration of endothelial cells into the tumor and this process further leads to tube formation and maturation of new microvessel. M2 TAMs promotes the proliferation of tumor cells directly by secreting growth factors, and participate in tumor progression by acting on endothelial cells, and thus promoting the neovascularization of the tumor .M2 TAMs are the key player during angiogenesis and promote each step of the angiogenesis cascade.. The angiogenic phenotype of macrophages is in part defined by their ability to secrete molecules that promote or inhibit angiogenesis . During tumor progression, M2 TAMs are migrated to tumors under the influence of various cytokines and growth factors secreted by cancer and stromal cells. However, it has been shown that M1 macrophages express IFN-γ, IL-1, and IL-6, which prime T-cell towards anti-tumor type-1 inflammatory r