Selective, α2β1 Integrin-Dependent Secretion of IL-6 by Connective Tissue Mast Cells

• Published in: Journal of innate immunity 2011, Vol.3 (5), p.459-470
• Main Authors: McCall-Culbreath, Karissa D., Li, Zhengzhi, Zhang, Zhonghua, Lu, Lucy X., Orear, Lynda, Zutter, Mary M.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Bacterial - immunology; Biological and medical sciences; Calcium Signaling - genetics; Calcium Signaling - immunology; Cell Degranulation; Cell physiology; Cells, Cultured; Connective Tissue - pathology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; General aspects; Genetics of the immune response; Humans; Immunity, Innate - genetics; Immunobiology; Immunoglobulin E - immunology; Immunoglobulin E - metabolism; Integrin alpha2beta1 - genetics; Integrin alpha2beta1 - immunology; Integrin alpha2beta1 - metabolism; Interleukin-6 - secretion; Listeria monocytogenes - immunology; Mast Cells - immunology; Mast Cells - metabolism; Mast Cells - pathology; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects); Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular and cellular biology; Receptor Aggregation; Research Article; Secretion. Exocytosis
• ISSN: 1662-811X; 1662-8128
• DOI: 10.1159/000324832

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 FcΕRI results in degranulation and the release of preformed, proinflammatory mediators including histamine and serotonin. We previously demonstrated that mast cell activation by Listeria monocytogenes requires the α2β1 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 α2β1 integrin-mediated mast cell release of preformed IL-6 without the concomitant release of histamine or β-hexosaminidase. α2β1 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, α2β1 integrin-dependent stimulation, providing the host with a specific innate immune response without stimulating an allergic reaction.