Signaling transduction pathways involved in basophil adhesion and histamine release

查看全文 作　　者：SHA [1,2,3]Quan;Lars K. [1]Poulsen;Jens [3]Gerwien;[3]NielsФdum;Per Stahl [1,4]Skov

机构地区：[1]Allergy Unit, National University Hospital, Copenhagen, Denmark;[2]Allergy and Immunology Research Center and Department of Medical Immunology, Anhui Medical University, Hefei 230032, China;[3]Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark;[4]Reference Laboratory, National University Hospital, Copenhagen, Denmark

出　　处：《Chinese Medical Journal》索引2006年第2期,共9页

基　　金：this study was supported by grants from the Danish Allergy Research Center, the Foundation for the Excellent Young Scientist of Anhui Province (No. 04043053) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry. 摘　　要：Background Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles of β1 andβ2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase (PI3K), src-kinases and extracellular signal regulated kinase (ERK)1/2 in basophil adhesion and histamine release (HR). Methods Basophils (purity of 10%-50%) were preincubated with anti-CD29 or anti-CD18 blocking antibodies before used for adhesion study. Basophils were preincubated with the pharmacological inhibitors wortmannin, PP1, PD98059 before used for adhesion and HR study. Cell adherence to bovine serum albumin (BSA) or fibronectin (Fn) was monitored using cell associated histamine as a basophil marker and the histamine was measured by the glass fiber assay. Results Basophil spontaneous adhesion to Fn was inhibited by anti-CD29. Interleukin (IL)-3, granulocyte/macrophage colony stimulating factor (GM-CSF) induced adhesion to BSA was inhibited by anti-CD18. Wortmannin at 1 μmol/L and PP1 at 20 μmol/L strongly interfered with, whereas PD98059 at 50 μmol/L weakly inhibited basophil spontaneous adhesion to Fn. One μmol/L wortmannin strongly inhibited IL-3, IL-5, GM-CSF and anti-IgE induced adhesion to BSA. PP1 at 20 μmol/L partly inhibited anti-IgE induced adhesion. Fifty μmol/L PD98059 marginally inhibited IL-5, weakly inhibited anti-IgE, partly inhibited GM-CSF induced adhesion. Wortmannin, PP1 and PD98059 inhibited anti-IgE (1:100 or 1:1000) induced basophil HR in a dose dependent manner. They inhibited calcium ionophore A23187 (10 μmol/L, 5 μmol/L) induced basophil HR in a dose dependent manner, but to different extend with PP1 being the most efficient. Conclusions Basophil spontaneous adhesion to Fn is mediated by β1-integrins whereas cytokine induced adhesion to BSA is mediated by β2-integrins. PI3K, src-kinases and ERK1/2 play distinct signaling roles in basophil adhesion and HR. PI3K is the key player whileERK1/2 is the weakest participant. 关键词：信号转导嗜碱细胞组氨释放医学研究

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Signaling transduction pathways involved in basophil adhesion and histamine release

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