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Biomedical subjects

Brian T Edelson

Publications and source records attributed to Brian T Edelson.

5 recordsLinked to original sources
PubMed2005

Novel collectin/C1q receptor mediates mast cell activation and innate immunity.

Mast cells play a critical role in innate immunity, allergy, and autoimmune diseases. The receptor/ligand interactions that mediate mast cell activation are poorly defined. The alpha2beta1 integrin, a receptor for collagens, laminins, decorin, E-cadherin, matrix metalloproteinase-1 (MMP-1), endorepellin, and several viruses, has been implicated in normal developmental, inflammatory, and oncogenic processes. We recently reported that alpha2 integrin subunit-deficient mice exhibited markedly diminished neutrophil and IL-6 responses during Listeria monocytogenes- and zymosan-induced peritonitis. Peritoneal mast cells require alpha2beta1 integrin expression for activation in response to pathogens, yet the ligand and molecular mechanisms by which the alpha2beta1 integrin induces activation and cytokine secretion remain unknown. We now report that the alpha2beta1 integrin is a novel receptor for multiple collectins and the C1q complement protein. We demonstrate that the alpha2beta1 integrin provides a costimulatory function required for mast cell activation and cytokine secretion. This finding suggests that the alpha2beta1 integrin is not only important for innate immunity but may serve as a critical target for the regulation of autoimmune/allergic disorders.

Animals↗
PubMed2003

Mast cell-mediated inflammatory responses require the alpha 2 beta 1 integrin.

Although the alpha 2 beta 1 integrin is widely expressed and has been extensively studied, it has not been previously implicated in mast cell biology. We observed that alpha 2 integrin subunit-deficient mice exhibited markedly diminished neutrophil and interleukin-6 responses during Listeria monocytogenes- and zymosan-induced peritonitis. Since exudative neutrophils of wild-type mice expressed little alpha 2 beta 1 integrin, it seemed unlikely that this integrin mediated neutrophil migration directly. Here, we demonstrate constitutive alpha 2 beta 1 integrin expression on peritoneal mast cells. Although alpha 2-null mice contain normal numbers of peritoneal mast cells, these alpha 2-null cells do not support in vivo mast cell-dependent inflammatory responses. We conclude that alpha 2 beta 1 integrin provides a costimulatory function required for mast cell activation and cytokine production in response to infection.

Animals↗
PubMed2002

MyD88-dependent but Toll-like receptor 2-independent innate immunity to Listeria: no role for either in macrophage listericidal activity.

We have assessed the requirements for Toll-like receptor (TLR) signaling in vivo during early infection with Listeria monocytogenes. Mice deficient for TLR2, a receptor required for the recognition of Gram-positive peptidoglycan, showed equivalent Listeria resistance to wild-type mice. However, mice deficient for MyD88, an adaptor molecule used by all TLRs, showed profound susceptibility with 3-4 logs greater Listeria burden and severe spleen and liver pathology at day 3 postinfection. Listeria-infected MyD88-deficient mice also showed markedly diminished IFN-gamma, TNF-alpha, and NO responses, despite evidence of macrophage activation and up-regulation of MHC class II molecules. We demonstrate that although minor MyD88-independent responses to live Listeria do occur, these are insufficient for normal host defense. Lastly, we performed experiments in vitro in which macrophages deficient in TLR2 or MyD88 were directly infected with Listeria: Although TLR signaling was required for macrophage NO and cytokine production in response to Listeria, handling and direct killing of Listeria by activated macrophages occurred by TLR2- and MyD88-independent mechanisms.

Adaptor Proteins, Signal Transducing↗