title: Tetraspanin CD151 Is a Negative Regulator of FcεRI-Mediated Mast Cell Activation.
abstract: Mast cells are critical in the pathogenesis of allergic disease due to the release of preformed and newly synthesized mediators, yet the mechanisms controlling mast cell activation are not well understood. Members of the tetraspanin family are recently emerging as modulators of FcεRI-mediated mast cell activation; however, mechanistic understanding of their function is currently lacking. The tetraspanin CD151 is a poorly understood member of this family and is specifically induced on mouse and human mast cells upon FcεRI aggregation but its functional effects are unknown. In this study, we show that CD151 deficiency significantly exacerbates the IgE-mediated late phase inflammation in a murine model of passive cutaneous anaphylaxis. Ex vivo, FcεRI stimulation of bone marrow-derived mast cells from CD151(-/-) mice resulted in significantly enhanced expression of proinflammatory cytokines IL-4, IL-13, and TNF-α compared with wild-type controls. However, FcεRI-induced mast cell degranulation was unaffected. At the molecular signaling level, CD151 selectively regulated IgE-induced activation of ERK1/2 and PI3K, associated with cytokine production, but had no effect on the phospholipase Cγ1 signaling, associated with degranulation. Collectively, our data indicate that CD151 exerts negative regulation over IgE-induced late phase responses and cytokine production in mast cells.
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and.
authors.forename: Hiam
authors.initials: H
authors.lastname: Abdala-Valencia
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bryce
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Wechsler
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and.
authors.forename: Lucas F
authors.initials: LF
authors.lastname: Loffredo
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Cook-Mills
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Hsu
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and s-berdnikovs@northwestern.edu.
authors.forename: Sergejs
authors.initials: S
authors.lastname: Berdnikovs
mesh_terms: D000707:Anaphylaxis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D015550:Cell Degranulation / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology; D056747:Immunomodulation; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010323:Passive Cutaneous Anaphylaxis; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction; D060185:Tetraspanin 24 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D017455:Receptors, IgE; D060185:Tetraspanin 24; D007073:Immunoglobulin E; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt