Editing Macrophage (section)

==== Chemical secretion ====
Recognition of MAMPs by PRRs can activate tissue resident macrophages to secrete proinflammatory cytokines that recruit other immune cells. Among the PRRs, TLRs play a major role in signal transduction leading to cytokine production.<ref name="Fu-2021" /> The binding of MAMPs to TLR triggers a series of downstream events that eventually activates transcription factor [[NF-κB]] and results in transcription of the genes for several proinflammatory cytokines, including [[Interleukin 1 beta|IL-1β]], [[Interleukin 6|IL-6]], [[Tumor necrosis factor|TNF-α]], [[Interleukin-12 subunit beta|IL-12B]], and [[Interferon type I|type I interferons]] such as IFN-α and IFN-β.<ref>{{cite journal | vauthors = Liu T, Zhang L, Joo D, Sun SC | title = NF-κB signaling in inflammation | journal = Signal Transduction and Targeted Therapy | volume = 2 | issue = 1 | pages = 17023– | date = 2017-07-14 | pmid = 29158945 | pmc = 5661633 | doi = 10.1038/sigtrans.2017.23 }}</ref> Systemically, IL-1β, IL-6, and TNF-α induce fever and initiate the acute phase response in which the liver secretes [[Acute-phase protein|acute phase proteins]].<ref name="Arango Duque-2014" /><ref name="Punt-2018"/><ref name="Murphy-2022">{{Cite book | vauthors = Murphy K, Weaver C, Berg L |title=Janeway's Immunobiology  |publisher=W. W. Norton & Company |year=2022 |isbn=978-0-393-88487-6 |edition=10th |location=New York, New York |language=en}}</ref> Locally, IL-1β and TNF-α cause vasodilation, where the gaps between blood vessel epithelial cells widen, and upregulation of cell surface adhesion molecules on epithelial cells to induce [[leukocyte extravasation]].<ref name="Arango Duque-2014" /><ref name="Punt-2018"/> Additionally, activated macrophages have been found to have delayed synthesis of [[prostaglandin]]s (PGs) which are important mediators of inflammation and pain. Among the PGs, anti-inflammatory [[Prostaglandin E2|PGE2]] and pro-inflammatory [[Prostaglandin D2|PGD2]] increase the most after activation, with PGE2 increasing expression of [[Interleukin 10|IL-10]] and inhibiting production of TNFs via the [[Cyclooxygenase-2|COX-2]] pathway.<ref>{{cite journal | vauthors = Tang T, Scambler ET, Smallie T, Cunliffe HE, et al. | title = Macrophage responses to lipopolysaccharide are modulated by a feedback loop involving prostaglandin E2, dual specificity phosphatase 1 and tristetraprolin | journal = Scientific Reports | volume = 7 | issue = 4350 | date = 2017-07-28 | page = 4350 | pmid = 28659609 | pmc = 5489520 | doi = 10.1038/s41598-017-04100-1 }}</ref><ref>{{cite journal |author5-link=Nada Abumrad | vauthors = Hu X, Cifarelli V, Sun S, Kuda O, Abumrad NA, Su X | title = Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment | journal = Journal of Lipid Research | volume = 57 | issue = 4 | pages = 663–73 | date = 2016-02-24 | pmid = 26912395 | pmc = 4808775 | doi = 10.1194/jlr.m066530 | doi-access = free }}</ref>

[[Neutrophil]]s are among the first immune cells recruited by macrophages to exit the blood via extravasation and arrive at the infection site.<ref name="Murphy-2022"/> Macrophages secrete many [[chemokine]]s such as [[CXCL1]], [[CXCL2]], and [[Interleukin 8|CXCL8 (IL-8)]] that attract neutrophils to the site of infection.<ref name="Arango Duque-2014" /><ref name="Murphy-2022"/> After neutrophils have finished phagocytosing and clearing the antigen at the end of the immune response, they undergo apoptosis, and macrophages are recruited from blood monocytes to help clear apoptotic debris.<ref>{{cite journal | vauthors = Eming SA, Krieg T, Davidson JM | title = Inflammation in wound repair: molecular and cellular mechanisms | journal = The Journal of Investigative Dermatology | volume = 127 | issue = 3 | pages = 514–525 | date = March 2007 | pmid = 17299434 | doi = 10.1038/sj.jid.5700701 | doi-access = free }}</ref>

Macrophages also recruit other immune cells such as monocytes, dendritic cells, natural killer cells, basophils, eosinophils, and T cells through chemokines such as [[CCL2]], [[CCL4]], [[CCL5]], [[Interleukin 8|CXCL8]], [[CXCL9]], [[CXCL10]], and [[CXCL11]].<ref name="Arango Duque-2014" /><ref name="Murphy-2022"/> Along with dendritic cells, macrophages help activate [[Natural killer cell|natural killer (NK) cells]] through secretion of [[Interferon type I|type I interferons]] (IFN-α and IFN-β) and [[Interleukin 12|IL-12]]. IL-12 acts with [[Interleukin 18|IL-18]] to stimulate the production of proinflammatory cytokine [[interferon gamma]] (IFN-γ) by NK cells, which serves as an important source of IFN-γ before the adaptive immune system is activated.<ref name="Murphy-2022"/><ref>{{cite journal | vauthors = Mezouar S, Mege JL | title = Changing the paradigm of IFN-γ at the interface between innate and adaptive immunity: Macrophage-derived IFN-γ | journal = Journal of Leukocyte Biology | volume = 108 | issue = 1 | pages = 419–426 | date = July 2020 | pmid = 32531848 | doi = 10.1002/JLB.4MIR0420-619RR | s2cid = 219622032 }}</ref> IFN-γ enhances the innate immune response by inducing a more aggressive phenotype in macrophages, allowing macrophages to more efficiently kill pathogens.<ref name="Murphy-2022"/>

Some of the T cell chemoattractants secreted by macrophages include [[CCL5]], [[CXCL9]], [[CXCL10]], and [[CXCL11]].<ref name="Arango Duque-2014" />