Complement protein C1q and adiponectin stimulate Mer tyrosine kinase dependent engulfment of apoptotic cells through a shared pathway

Manuel D Galvan; Holly Hulsebus; Thomas Heitker; Erliang Zeng; Suzanne S Bohlson

doi:10.1159/000363295

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Complement protein C1q and adiponectin stimulate Mer tyrosine kinase dependent engulfment of apoptotic cells through a shared pathway

Journal article

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Complement protein C1q and adiponectin stimulate Mer tyrosine kinase dependent engulfment of apoptotic cells through a shared pathway

Manuel D Galvan, Holly Hulsebus, Thomas Heitker, Erliang Zeng and Suzanne S Bohlson

Journal of innate immunity, Vol.6(6), pp.780-792

2014

DOI: 10.1159/000363295

PMCID: PMC4201872

PMID: 24942043

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Abstract

The failure to clear apoptotic cells is linked to defects in development and autoimmunity. Complement component C1q is required for efficient engulfment of apoptotic cells (efferocytosis), and C1q deficiency leads to development of lupus. We recently identified a novel molecular mechanism for C1q-dependent efferocytosis in murine macrophages. C1q elicited the expression of Mer tyrosine kinase; a receptor that regulates efficient efferocytosis and prevention of autoimmunity. To characterize the C1q–dependent signal transduction mechanism, pathway analysis of the transcriptome from C1q–activated macrophages was performed, and it identified the adiponectin signaling pathway as significantly upregulated with C1q. Adiponectin is structurally homologous to C1q and regulates cellular metabolism via downstream activation of AMP-activated protein kinase (AMPK). Macrophage stimulation with C1q resulted in activation of AMPK, and silencing of AMPK expression using siRNA inhibited C1q–dependent efferocytosis. Adiponectin signaling also stimulates activation of nuclear receptors, and inhibition of the nuclear receptor retinoid x receptor abrogated C1q–dependent Mer expression and efferocytosis. Furthermore, adiponectin elicited Mer expression and Mer-dependent efferocytosis in macrophages similar to cells stimulated with C1q. Collectively, our results suggest that C1q and adiponectin share a common signal transduction cascade to promote clearance of apoptotic cells, and identify a novel molecular pathway required for efficient efferocytosis.

Details

Title: Subtitle: Complement protein C1q and adiponectin stimulate Mer tyrosine kinase dependent engulfment of apoptotic cells through a shared pathway
Creators: Manuel D Galvan - Department of Microbiology and Immunology, Des Moines University, Des Moines, IA
Holly Hulsebus - Department of Microbiology and Immunology, Des Moines University, Des Moines, IA
Thomas Heitker - Department of Microbiology and Immunology, Indiana University School of Medicine - South Bend, South Bend, IN
Erliang Zeng - Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN
Suzanne S Bohlson - Department of Microbiology and Immunology, Des Moines University, Des Moines, IA
Resource Type: Journal article
Publication Details: Journal of innate immunity, Vol.6(6), pp.780-792
DOI: 10.1159/000363295
PMID: 24942043
PMCID: PMC4201872
NLM abbreviation: J Innate Immun
ISSN: 1662-811X
eISSN: 1662-8128
Language: English
Date published: 2014
Academic Unit: Preventive and Community Dentistry; Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Biostatistics; Dental Research
Record Identifier: 9984065368802771

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