Selective, alpha 2 beta 1 Integrin-Dependent Secretion of IL-6 by Connective Tissue Mast Cells

作者：McCall Culbreath Karissa D; Li Zhengzhi; Zhang Zhonghua; Lu Lucy X; Orear Lynda; Zutter Mary M^*

来源：Journal of Innate Immunity, 2011, 3(5): 459-470.

DOI：10.1159/000324832

• Adhesion molecules
• Cytokines
• Host defense
• Integrin
• Mast cell

Mast cells, critical mediators of inflammation and anaphylaxis, are poised as one of the first lines of defense against external assault. Mast cells release several classes of preformed and de novo synthesized mediators. Cross-linking of the high-affinity Fc epsilon RI results in degranulation and the release of preformed, proinflamnnatory mediators including histamine and serotonin. We previously demonstrated that mast cell activation by Listeria monocyto genes requires the alpha 2 beta 1 integrin for rapid IL-6 secretion both in vivo and in vitro. However, the mechanism of IL-6 release is unknown. Here, we demonstrate the Listeria- and alpha 2 beta 1 integrin-mediated mast cell release of preformed IL-6 without the concomitant release of histamine or beta-hexosaminidase. alpha 2 beta 1 integrin-dependent mast cell activation and IL-6 release is calcium independent. In contrast, IgE cross-linking-mediated degranulation is calcium dependent and does not result in IL-6 release, demonstrating that distinct stimuli result in the release of specific mediator pools. These studies demonstrate that IL-6 is presynthesized and stored in connective tissue mast cells and can be released from mast cells in response to distinct, alpha 2 beta 1 integrin-dependent stimulation, providing the host with a specific innate immune response without stimulating an allergic reaction.

• 出版日期2011