Chronically KIT-stimulated clonally-derived human mast cells show heterogeneity in different tissue microenvironments.
Chronically KIT-stimulated clonally-derived human mast cells show heterogeneity in different tissue microenvironments.
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长期 KIT 刺激的克隆来源的人类肥大细胞在不同的组织微环境中表现出异质性。
DOI：
10.1111/1523-1747.ep12292240
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Murphy,GF
中科院分区：
文献类型：
--
作者：
Longley,BJ;Tyrrell,L;Lu,S;Ma,Y;Klump,V;Murphy,GF
人肥大细胞前体在骨髓中产生并循环到不同的组织微环境，在那里它们发展出不同的表型，其特征可能在于丝氨酸蛋白酶，糜酶的差异表达。肥大细胞的生长和发育受到肥大细胞生长因子的刺激，肥大细胞生长因子也被称为kit配体，因为其专性受体是KIT，即c-KIT原癌基因的蛋白产物。KIT-kit配体轴对人肥大细胞表型的体内影响尚未确定。我们用免疫组织化学方法检测了色素性荨麻疹和侵袭性系统性肥大细胞增多症患者肥大细胞类胰蛋白酶和糜蛋白酶的原位表达，其病理性肥大细胞是克隆来源的，长期受到KIT的刺激，因为它们都含有相同的点突变，导致KIT的组成性激活。肥大细胞在脾脏和皮肤表达类胰蛋白酶，但只有在皮肤中的大多数肥大细胞表达糜酶。我们的结论是，慢性刺激的KIT-kit配体轴并不必然承诺肥大细胞的凝乳酶阳性或凝乳酶阴性的表型。这些发现表明，在决定肥大细胞表型的因素，而不是试剂盒配体占主导地位。
Human mast cell precursors arise in the bone marrow and circulate to different tissue microenvironments, where they develop distinct phenotypes that may be characterized by differential expression of the serine protease, chymase. The growth and development of mast cells is stimulated by mast cell growth factor, which is also known as kit ligand because its obligate receptor is KIT, the protein product of the c-KITproto-oncogene. Thein vivoinfluence of the KIT-kit ligand axis on the phenotype of human mast cells has not been determined. We used immunohistochemistry to detectin situexpression of tryptase and chymase by mast cells of a patient with urticaria pigmentosa and aggressive systemic mastocytosis, whose pathologic mast cells are clonally derived and chronically stimulated by KIT because they all contain the same point mutation causing constitutive activation of KIT. Mast cells in both spleen and skin expressed tryptase, but only in the skin did a majority of mast cells express chymase. We conclude that chronic stimulation of the KIT-kit ligand axis does not irrevocably commit mast cells to a chymase-positive or chymase-negative phenotype. These findings suggest that factors other than kit ligand predominate in determining mast cell phenotype.