Hernandez-Hansen Valerie, Mackay Graham A, Lowell Clifford A, Wilson Bridget S, Oliver Janet M
Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, CRF Rm. 205, 2325 Camino De Salud NE, Albuquerque, NM 87131, USA.
J Leukoc Biol. 2004 Jan;75(1):143-51. doi: 10.1189/jlb.0503224. Epub 2003 Oct 2.
Previous investigators have reported that deletion of the protein tyrosine kinase Lyn alters mast cell (MC) signaling responses but does not affect or reduces the cytokine-mediated proliferation of mouse bone marrow-derived MC (BMMC) precursors and of mature MC. We observed that Lyn-deficient mice have more peritoneal MC than wild-type (WT) mice. Studies to explore this unexpected result showed that Lyn(-/-) BM cells expand faster than WT cells in response to interleukin (IL)-3 and stem-cell factor over the 4-5 weeks required to produce a >95% pure population of granular, receptor with high affinity for immunoglobulin E-positive BMMC. Furthermore, differentiated Lyn(-/-) BMMC continue to proliferate more rapidly than WT BMMC and undergo less apoptosis in response to cytokine withdrawal. Additionally, Lyn(-/-) BMMC support greater IL-3-mediated phosphorylation of the prosurvival kinase, Akt, and the proliferative kinase, extracellular-regulated kinase 1/2. These results identify Lyn as a negative regulator of murine MC survival and proliferation.
先前的研究人员报告称，蛋白酪氨酸激酶Lyn的缺失会改变肥大细胞（MC）的信号反应，但不影响或减少细胞因子介导的小鼠骨髓来源的MC（BMMC）前体细胞和成熟MC的增殖。我们观察到，Lyn缺陷小鼠的腹膜MC比野生型（WT）小鼠更多。为探究这一意外结果而开展的研究表明，在产生>95%纯度的对免疫球蛋白E呈高亲和力的颗粒状受体阳性BMMC所需的4-5周时间里，Lyn（-/-）骨髓细胞对白细胞介素（IL）-3和干细胞因子的反应比WT细胞扩增得更快。此外，分化后的Lyn（-/-）BMMC继续比WT BMMC增殖得更快，并且在细胞因子撤除后经历的凋亡更少。另外，Lyn（-/-）BMMC支持促生存激酶Akt和增殖激酶细胞外调节激酶1/2的更多IL-3介导的磷酸化。这些结果确定Lyn是小鼠MC存活和增殖的负调节因子。
