Weiss R R, Whitaker-Menezes D, Longley J, Bender J, Murphy G F
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia.
J Invest Dermatol. 1995 Jan;104(1):101-6. doi: 10.1111/1523-1747.ep12613587.
Mast cell growth factor (MGF), a molecule that serves as a ligand for the receptor tyrosine kinase c-kit, is important in mast cell differentiation, migration, and activation. Previous studies of paraffin-embedded human skin using antibody to murine MGF and reverse transcription-polymerase chain reaction have demonstrated MGF protein and mRNA expression in keratinocytes and isolated dermal cells. We utilized a monoclonal antibody to human MGF to further define patterns of immunoreactivity in frozen specimens of neonatal and adult skin from normal individuals and from patients with urticaria pigmentosa. In addition to keratinocytes and isolated dermal cells in normal and urticaria pigmentosa skin, MGF was detected in cells lining superficial and mid-dermal vessels. Co-expression of MGF and the vascular antigen CD31, and immunoelectron microscopy, identified MGF-positive cells as endothelial cells. Patterns of endothelial MGF expression were not influenced by mast cell degranulation and endothelial E-selectin induction in vitro. By ultrastructure, unfixed specimens demonstrated MGF expression both within the endothelial cytoplasm and in association with lumenal, but not ablumenal, surfaces. Specimens fixed with Nakane's solution had diminished endothelial cytoplasmic MGF reactivity, but lumenal expression was maintained, suggesting persistence of a membrane-associated reactivity. MGF mRNA was also detected in cultured dermal microvascular endothelial cells using reverse transcription-polymerase chain reaction. These data establish human dermal endothelial cells as sites of MGF production and expression in human skin. Mast cell precursors must home to skin via vascular channels and differentiate in the immediate perivascular space. Thus, endothelial MGF may be an important determinant of adhesion and differentiation of mast cell progenitors expressing receptors for MGF.
肥大细胞生长因子（MGF）是一种作为受体酪氨酸激酶c-kit配体的分子，在肥大细胞的分化、迁移和激活过程中发挥着重要作用。先前利用抗鼠MGF抗体及逆转录-聚合酶链反应对石蜡包埋的人皮肤进行研究，已证实角质形成细胞和分离的真皮细胞中有MGF蛋白及mRNA表达。我们利用抗人MGF单克隆抗体，进一步明确正常个体及色素性荨麻疹患者的新生儿和成人皮肤冰冻标本中的免疫反应模式。除了正常及色素性荨麻疹皮肤中的角质形成细胞和分离的真皮细胞外，在浅表和真皮中层血管的内皮细胞中也检测到了MGF。MGF与血管抗原CD31的共表达以及免疫电镜检查确定MGF阳性细胞为内皮细胞。体外肥大细胞脱颗粒和内皮E选择素诱导并不影响内皮MGF的表达模式。超微结构显示，未固定标本在内皮细胞质内及与管腔面而非管腔外表面相关处均有MGF表达。用中根氏溶液固定的标本内皮细胞质MGF反应性减弱，但管腔表达得以保留，提示存在一种与膜相关的反应性。利用逆转录-聚合酶链反应在培养的真皮微血管内皮细胞中也检测到了MGF mRNA。这些数据证实人真皮内皮细胞是人体皮肤中MGF产生和表达的部位。肥大细胞前体必须通过血管通道归巢至皮肤，并在紧邻血管周围的空间内分化。因此，内皮MGF可能是表达MGF受体的肥大细胞祖细胞黏附与分化的重要决定因素。
