Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. Export

@article{citeulike:5894077, abstract = {Apoptosis in vivo is followed almost inevitably by rapid uptake into adjacent phagocytic cells, a critical process in tissue remodeling, regulation of the immune response, or resolution of inflammation. Phagocytosis of apoptotic cells by macrophages has been suggested to be a quiet process that does not lead to production of inflammatory mediators. Here we show that phagocytosis of apoptotic neutrophils (in contrast to immunoglobulin G-opsonized apoptotic cells) actively inhibited the production of interleukin (IL)-1beta, IL-8, IL-10, granulocyte macrophage colony-stimulating factor, and tumor necrosis factor-alpha, as well as leukotriene C4 and thromboxane B2, by human monocyte-derived macrophages. In contrast, production of transforming growth factor (TGF)-beta1, prostaglandin E2, and platelet-activating factor (PAF) was increased. The latter appeared to be involved in the inhibition of proinflammatory cytokine production because addition of exogenous TGF-beta1, prostaglandin E2, or PAF resulted in inhibition of lipopolysaccharide-stimulated cytokine production. Furthermore, anti-TGF-beta antibody, indomethacin, or PAF receptor antagonists restored cytokine production in lipopolysaccharide-stimulated macrophages that had phagocytosed apoptotic cells. These results suggest that binding and/or phagocytosis of apoptotic cells induces active antiinflammatory or suppressive properties in human macrophages. Therefore, it is likely that resolution of inflammation depends not only on the removal of apoptotic cells but on active suppression of inflammatory mediator production. Disorders in either could result in chronic inflammatory diseases.}, author = {Fadok, V. A. and Bratton, D. L. and Konowal, A. and Freed, P. W. and Westcott, J. Y. and Henson, P. M.}, citeulike-article-id = {5894077}, citeulike-linkout-0 = {http://dx.doi.org/10.1172/JCI1112}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/9466984}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=9466984}, comment = {Is it possible then that: * Macrophages are present during involution - not as a primary innate inflammatory agent but to devour the apoptotic residues and prevent overt inflammation/inflammatory mediators from accumulating in the microenvironment. * The lack of presence of these macrophages can lead to a chronic inflammatory environment? * What do we know about the prognosis of tumours with a vast amount of macrophages onsite? * How do we know which macrophages are there to devour apoptotic cells and which have come to join the random innate immune battle?}, day = {15}, doi = {10.1172/JCI1112}, issn = {0021-9738}, journal = {The Journal of clinical investigation}, keywords = {apoptosis, inflammation, interesting, macrophage}, month = {February}, number = {4}, pages = {890--898}, posted-at = {2009-10-06 01:19:19}, priority = {2}, title = {Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.}, url = {http://dx.doi.org/10.1172/JCI1112}, volume = {101}, year = {1998} }

TY - JOUR ID - citeulike:5894077 L3 - citeulike-article-id:5894077 N2 - Apoptosis in vivo is followed almost inevitably by rapid uptake into adjacent phagocytic cells, a critical process in tissue remodeling, regulation of the immune response, or resolution of inflammation. Phagocytosis of apoptotic cells by macrophages has been suggested to be a quiet process that does not lead to production of inflammatory mediators. Here we show that phagocytosis of apoptotic neutrophils (in contrast to immunoglobulin G-opsonized apoptotic cells) actively inhibited the production of interleukin (IL)-1beta, IL-8, IL-10, granulocyte macrophage colony-stimulating factor, and tumor necrosis factor-alpha, as well as leukotriene C4 and thromboxane B2, by human monocyte-derived macrophages. In contrast, production of transforming growth factor (TGF)-beta1, prostaglandin E2, and platelet-activating factor (PAF) was increased. The latter appeared to be involved in the inhibition of proinflammatory cytokine production because addition of exogenous TGF-beta1, prostaglandin E2, or PAF resulted in inhibition of lipopolysaccharide-stimulated cytokine production. Furthermore, anti-TGF-beta antibody, indomethacin, or PAF receptor antagonists restored cytokine production in lipopolysaccharide-stimulated macrophages that had phagocytosed apoptotic cells. These results suggest that binding and/or phagocytosis of apoptotic cells induces active antiinflammatory or suppressive properties in human macrophages. Therefore, it is likely that resolution of inflammation depends not only on the removal of apoptotic cells but on active suppression of inflammatory mediator production. Disorders in either could result in chronic inflammatory diseases. IS - 4 JF - The Journal of clinical investigation SN - 0021-9738 EP - 898 TI - Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. VL - 101 SP - 890 KW - apoptosis KW - inflammation KW - interesting KW - macrophage N1 - Is it possible then that: * Macrophages are present during involution - not as a primary innate inflammatory agent but to devour the apoptotic residues and prevent overt inflammation/inflammatory mediators from accumulating in the microenvironment. * The lack of presence of these macrophages can lead to a chronic inflammatory environment? * What do we know about the prognosis of tumours with a vast amount of macrophages onsite? * How do we know which macrophages are there to devour apoptotic cells and which have come to join the random innate immune battle? AU - Fadok, VA AU - Bratton, DL AU - Konowal, A AU - Freed, PW AU - Westcott, JY AU - Henson, PM PY - 1998/02/15/ UR - http://dx.doi.org/10.1172/JCI1112 ER -