Cultured peripheral blood mast cells from chronic idiopathic urticaria patients spontaneously degranulate upon IgE sensitization: Relationship to expression of Syk and SHIP-2.
Recently, signaling changes in the FcvarepsilonRI pathway involving inositol lipid phosphatases have been identified in the basophils of chronic idiopathic urticaria (CIU) subjects. Based on the profile of basophil FcvarepsilonRI-mediated histamine degranulation, we have segregated CIU subjects into two groups, CIU Responder (CIU R) or CIU Nonresponder (CIU NR). In the present study, we compared expression of SHIP-1, SHIP-2, and Syk protein to histamine release (HR) from mast cells (MC) cultured from the peripheral blood of CIU R, CIU NR, and normal subjects. The MC of CIU R donors contained significantly increased Syk and decreased SHIP-2 as compared to CIU NR (Syk: p=0.038, SHIP-2: p=0.038) and normals (Syk: p=0.042, SHIP-2: p=0.027). Spontaneous HR from CIU donors was increased two-fold compared to normals (p=0.04). In summary, our results suggest a possible predilection for urticarial MC to spontaneously degranulate upon IgE sensitization contributing to the increased pruritus associated with CIU.
Saini
Sarbjit S
SS
Department of Medicine, Division of Allergy and Clinical Immunology, The Johns Hopkins University School of Medicine, Baltimore MD 21224, USA.
Paterniti
Miya
M
Vasagar
Kavitha
K
Gibbons
Scott P
SP
Sterba
Patricia M
PM
Vonakis
Becky M
BM
D000328:Adult; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D000072181:Inositol Polyphosphate 5-Phosphatases; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000072377:Syk Kinase; D014581:Urticaria / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D007073:Immunoglobulin E; D006632:Histamine; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; C000606896:SYK protein, human; D000072377:Syk Kinase; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases