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Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-β1 secretion and the resolution of inflammation

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Huynh, Mai-Lan N., Fadok, Valerie A., Henson, Peter M.·2002·Journal of Clinical Investigation
DOI 10.1172/jci0211638
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Abstract

Ingestion of apoptotic cells in vitro by macrophages induces TGF-β1 secretion, resulting in an antiinflammatory effect and suppression of proinflammatory mediators.Here, we show in vivo that direct instillation of apoptotic cells enhanced the resolution of acute inflammation.This enhancement appeared to require phosphatidylserine (PS) on the apoptotic cells and local induction of TGF-β1.Working with thioglycollate-stimulated peritonea or LPS-stimulated lungs, we examined the effect of apoptotic cell uptake on TGF-β1 induction.Viable or opsonized apoptotic human Jurkat T cells, or apoptotic PLB-985 cells, human monomyelocytes that do not express PS during apoptosis, failed to induce TGF-β1.PS liposomes, or PS directly transferred onto the PLB-985 surface membranes, restored the TGF-β1 induction.Apoptotic cell instillation into LPS-stimulated lungs reduced proinflammatory chemokine levels in the bronchoalveolar lavage fluid (BALF).Additionally, total inflammatory cell counts in the BALF were markedly reduced 1-5 days after apoptotic cell instillation, an effect that could be reversed by opsonization or coinstillation of TGF-β1 neutralizing antibody.This reduction resulted from early decrease in neutrophils and later decreases in lymphocytes and macrophages.In conclusion, apoptotic cell recognition and clearance, via exposure of PS and ligation of its receptor, induce TGF-β1 secretion, resulting in accelerated resolution of inflammation.

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Metadata

Authors
Huynh, M.-L. N., Fadok, V. A., & Henson, P. M.
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2002-01-01
Volume
109
Issue
1
Pages
41-50
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci0211638
OpenAlex
W4235300003
Cited by
957
References
2
FWCI
16.40
Type
journal article
Language
en
Open access
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CoChat. (2026). Citation check: Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-β1 secretion and the resolution of inflammation. https://app.cochat.ai/papers/10.1172/jci0211638
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Huynh, M.-L. N., Fadok, V. A., & Henson, P. M. (2002). Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-β1 secretion and the resolution of inflammation. Journal of Clinical Investigation. https://doi.org/10.1172/jci0211638

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