Cultured peripheral blood mast cells from chronic idiopathic urticaria patients spontaneously degranulate upon IgE sensitization: Relationship to expression of Syk and SHIP-2

• Published in: Clinical immunology (Orlando, Fla.) Vol. 132; no. 3; pp. 342 - 348
• Main Authors: Saini, Sarbjit S., Paterniti, Miya, Vasagar, Kavitha, Gibbons, Scott P., Sterba, Patricia M., Vonakis, Becky M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.09.2009; Elsevier
• Subjects: Adult; Allergic diseases; Allergy and Immunology; Antibodies - immunology; Antibodies - pharmacology; Biological and medical sciences; CD34 + stem cell; Cell Degranulation - drug effects; Cell Degranulation - immunology; Degranulation; FcɛRI; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histamine; Histamine - metabolism; Humans; Immunoglobulin E; Immunoglobulin E - immunology; Immunopathology; Inositol; Inositol Polyphosphate 5-Phosphatases; Intracellular Signaling Peptides and Proteins - metabolism; Leukocytes (basophilic); Lipids; Male; Mast cell; Mast cells; Mast Cells - cytology; Mast Cells - immunology; Mast Cells - metabolism; Medical sciences; Middle Aged; Peripheral blood; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; Phosphoric Monoester Hydrolases - metabolism; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins c-kit - metabolism; Receptors, IgE - metabolism; Signal transduction; Signal Transduction - immunology; Skin allergic diseases. Stinging insect allergies; Syk Kinase; Syk protein; Urticaria; Urticaria - immunology; Urticaria - metabolism; Syk; FcɛRI; Urticaria; HR; CIU; Signal transduction; PI 3,4,5 P 3; CIU R; CIU NR; MC; SHIP; Mast cell; HRF; CD34 + stem cell; Src homology 2 (SH2)-containing inositol phosphatase; CIU anti-IgE non-responder; Histamine release; Chronic idiopathic urticaria; Spleen tyrosine kinase; Histamine Releasing Factor; Phosphatidylinositol 3,4,5 trisphosphate concentration; FcεRI; CIU anti-IgE responder; Human; Cell culture; Skin disease; Enzyme; Transferases; Stem cell; IgE; Idiopathic; FcεRI receptor; Immunoglobulin receptor; Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2; Hematopoietic cell; Cell subpopulation; Blood cell; Chronic; Immunology; Sensitization; Tyrosine protein kinase Syk; Protein-tyrosine kinase; CD34
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2009.05.003

Recently, signaling changes in the FcɛRI pathway involving inositol lipid phosphatases have been identified in the basophils of chronic idiopathic urticaria (CIU) subjects. Based on the profile of basophil FcɛRI-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 pruritis associated with CIU.