C1q and adiponectin trigger efferocytosis via a shared pathway (P1287)
| Autor: | Suzanne Bohlson, Manuel Galvan |
|---|---|
| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 190:63.1-63.1 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.190.supp.63.1 |
| Popis: | Failure to efficiently clear apoptotic cells (efferocytosis) is associated with autoimmunity. Complement component C1q is required for efferocytosis, and deficiency in C1q leads to development of autoimmunity. We recently identified a novel molecular mechanism for C1q-dependent efferocytosis in mouse macrophages. We found that C1q elicited the expression and function of Mer tyrosine kinase and the Mer ligand, Ga6: a receptor-ligand pair that mediates efferocytosis. To define the signal transduction pathway downstream of C1q, pathway analysis was performed using the transcriptome from C1q-treated macrophages. This analysis revealed that the adiponectin signaling pathway was significantly upregulated with C1q. Adiponectin is a well characterized adipokine with critical roles in glucose and fatty acid metabolism, and it is structurally homologous to C1q. Similar to C1q, adiponectin triggered expression of Mer that correlated with enhanced engulfment of apoptotic cells, and a soluble Mer-Fc fusion protein inhibited adiponectin-dependent efferocytosis. Furthermore, C1q triggered activation of AMP kinase, a central regulator of adiponectin signaling and cellular metabolism. Inhibition of AMPK signaling resulted in inability to upregulate C1q-dependent Mer expression in macrophages. Our results suggest that C1q and adiponectin activate macrophages via a common signaling pathway, and this pathway may contribute to the molecular crosstalk between inflammation and metabolism. |
| Databáze: | OpenAIRE |
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