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Research Article Free access | 10.1172/JCI1112

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

V A Fadok, D L Bratton, A Konowal, P W Freed, J Y Westcott, and P M Henson

Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. Valerie_Fadok.PEDIATRICS@mac.njc.org

Find articles by Fadok, V. in: PubMed | Google Scholar

Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. Valerie_Fadok.PEDIATRICS@mac.njc.org

Find articles by Bratton, D. in: PubMed | Google Scholar

Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. Valerie_Fadok.PEDIATRICS@mac.njc.org

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Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. Valerie_Fadok.PEDIATRICS@mac.njc.org

Find articles by Freed, P. in: PubMed | Google Scholar

Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. Valerie_Fadok.PEDIATRICS@mac.njc.org

Find articles by Westcott, J. in: PubMed | Google Scholar

Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. Valerie_Fadok.PEDIATRICS@mac.njc.org

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Published February 15, 1998 - More info

Published in Volume 101, Issue 4 on February 15, 1998
J Clin Invest. 1998;101(4):890–898. https://doi.org/10.1172/JCI1112.
© 1998 The American Society for Clinical Investigation
Published February 15, 1998 - Version history
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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.

Version history
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