Crosstalk between the α2β1 integrin and c-met/HGF-R regulates innate immunity
| Autor: | Karissa D. McCall-Culbreath, Zhengzhi Li, Mary M. Zutter |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Immunology
Integrin Integrin alpha2 Biochemistry Autoimmune Diseases Collagen receptor Mice Immune system Bacterial Proteins Animals Listeriosis Internalin Immunologic Capping Mast Cells Immunobiology Inflammation Mice Knockout Extracellular Matrix Proteins Innate immune system biology Complement C1q Receptors IgG Membrane Proteins Cell Biology Hematology Proto-Oncogene Proteins c-met Listeria monocytogenes Immunity Innate Cell biology Integrin alpha M Leukocytes Mononuclear biology.protein Cytokines Receptors Virus Integrin beta 6 Protein Binding |
| Zdroj: | Blood. 111:3562-3570 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Data from several investigators suggest that the α2β1 integrin, a receptor for collagens, laminins, decorin, E-cadherin, matrix metalloproteinase-1, endorepellin, and several viruses, is required for innate immunity and regulation of autoimmune/allergic disorders. We demonstrated that the innate immune response to Listeria monocytogenes required α2β1 integrin expression by peritoneal mast cells (PMCs). Ligation of the α2β1 integrin by C1q contained in immune complexes comprised of Listeria and antibody was required for PMC activation in vitro and in vivo. However, ligation of the α2β1 integrin alone was insufficient to activate cytokine secretion, suggesting that one or more additional signals emanating from a coreceptor were required for PMC activation. Here, we demonstrate that C1q, but neither other complement proteins nor FcRγ, is required for early innate immune response to Listeria. The binding of Listeria's Internalin B (InlB) to hepatocyte growth factor receptor (HGF-R)/c-met provides the costimulatory function required for PMC activation. Either HGF or Listeria InlB bound to c-met and either C1q or type I collagen bound to α2β1 integrin stimulates PMC activation. These findings suggest that crosstalk between c-met and the α2β1 integrin may contribute to mast-cell activation in autoimmune and inflammatory disorders. |
| Databáze: | OpenAIRE |
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