title: Selective, α2β1 integrin-dependent secretion of il-6 by connective tissue mast cells.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tenn., USA.
authors.forename: Karissa D
authors.initials: KD
authors.lastname: McCall-Culbreath
authors.forename: Zhengzhi
authors.initials: Z
authors.lastname: Li
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Zhang
authors.forename: Lucy X
authors.initials: LX
authors.lastname: Lu
authors.forename: Lynda
authors.initials: L
authors.lastname: Orear
authors.forename: Mary M
authors.initials: MM
authors.lastname: Zutter
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D020013:Calcium Signaling / Q000235:genetics / Q000276:immunology; D015550:Cell Degranulation; D002478:Cells, Cultured; D003238:Connective Tissue / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D038982:Integrin alpha2beta1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011940:Receptor Aggregation
chemical_list: D000942:Antigens, Bacterial; D038982:Integrin alpha2beta1; D015850:Interleukin-6; D007073:Immunoglobulin E