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.
Edelson
Brian T
BT
Department of Pathology, Washington University School of Medicine, St Louis, MO, USA.
Stricker
Thomas P
TP
Li
Zhengzhi
Z
Dickeson
S Kent
SK
Shepherd
Virginia L
VL
Santoro
Samuel A
SA
Zutter
Mary M
MM
D000818:Animals; D000936:Antigen-Antibody Complex / Q000494:pharmacology; D037222:Collectins / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D007113:Immunity, Innate; D038982:Integrin alpha2beta1 / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism; D008024:Ligands; D008407:Mast Cells / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010537:Peritoneum / Q000166:cytology; D011485:Protein Binding; D011951:Receptors, Complement / Q000502:physiology*
D000936:Antigen-Antibody Complex; D037222:Collectins; D016207:Cytokines; D038982:Integrin alpha2beta1; D015850:Interleukin-6; D008024:Ligands; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; C032402:complement 1q receptor