A CD18‐dependent protein kinase C β‐mediated alternative cell death pathway of activated monocytes

Activated monocytes become resistant to numerous death stimuli including death receptors. Given that the uncontrolled activation of monocytes/macrophages and their persistence can lead to severe inflammatory conditions, it is critical to define the pathways that control their elimination. We previou...

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Bibliographic Details
Published in:International immunology 2002-09, Vol.14 (9), p.1003-1014
Main Authors: Castaigne, Jean‐Gabriel, Guo, Wenyan, Lévéille, Claire, Charron, Dominique, Al‐Daccak, Reem
Format: Article
Language:English
Subjects:
apoptosis
CD18 Antigens - physiology
Cell Death - physiology
Cell Line
Histocompatibility Antigens Class II - immunology
Histocompatibility Antigens Class II - physiology
HLA-DR Antigens - immunology
HLA-DR Antigens - physiology
Humans
integrins
Interferon-gamma - pharmacology
macrophages
MHC class II
Monocytes - drug effects
Monocytes - physiology
Precipitin Tests
Protein Kinase C - physiology
Protein Kinase C beta
protein tyrosine kinase
Signal Transduction
signaling
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Summary:Activated monocytes become resistant to numerous death stimuli including death receptors. Given that the uncontrolled activation of monocytes/macrophages and their persistence can lead to severe inflammatory conditions, it is critical to define the pathways that control their elimination. We previously reported that ligation of HLA‐DR molecules on peripheral blood‐derived monocytes induces their death. To investigate the mechanisms of HLA‐DR‐mediated death in monocytes, we used the THP‐1 monocytic cell line as a model. We show that while THP‐1 are equally resistant to HLA‐DR‐ and to Fas‐mediated death, treatment of THP‐1 with IFN‐γ renders them sensitive to HLA‐DR‐ but not to Fas‐mediated death. Both activation of the Src family protein tyrosine kinase and classical protein kinase C (PKC) occur through HLA‐DR, but only PKC activation is involved in HLA‐DR‐mediated death of these cells. Moreover, HLA‐DR‐mediated cell death of activated monocytes implicates a regulatory loop between the HLA‐DR/CD18 complex and the downstream activation of PKCβ. Thus, our study identifies an alternative physiological signaling pathway of monocyte death, and further investigation on its regulation is likely to provide significant insights into the control of monocyte homeostasis and inflammation.
ISSN:0953-8178
1460-2377
1460-2377
DOI:10.1093/intimm/dxf071