Meininger C J, Brightman S E, Kelly K A, Zetter B R
Department of Medical Physiology, Texas A&M University Health Science Center, College Station.
Lab Invest. 1995 Feb;72(2):166-73.
Capillary hemangiomas, the most common tumors in young children, consist of proliferating capillary vessels and endothelial cells. These tumors also contain large numbers of mast cells, compared with the normal surrounding skin or tissue. We have recently shown that stem cell factor (SCF), the gene product of the murine steel locus, can act as a chemoattractant for mast cells. In this study, we investigated whether SCF might be involved in the recruitment and maintenance of mast cells in hemangiomas.
Cultured endothelial cells derived from a murine hemangioma were compared with normal vascular endothelial cells for the ability to produce and release SCF, a mitogen for mast cells.
Conditioned medium from hemangioma-derived endothelial cells stimulated the proliferation of cultured mast cells. This proliferative activity was potentiated by interleukin-3. The same conditioned medium was unable to stimulate proliferation of mast cells expressing a defective receptor for SCF. The medium was also unable to stimulate proliferation when it was preincubated with neutralizing antibodies specific for SCF. Immunoprecipitation and Western blot analysis of the conditioned media from hemangioma cells and normal endothelial cells demonstrated the 31,000 molecular weight SCF in hemangioma-conditioned medium only. In addition, proliferative activity for mast cells could not be demonstrated in the conditioned medium of the normal endothelial cells, although Northern blot analysis indicated that both normal and hemangioma-derived endothelial cells express SCF mRNA. Reverse transcriptase-polymerase chain reaction techniques were used to amplify the DNA sequence coding for the proteolytic cleavage site used for release of SCF. Results indicated that both normal and hemangioma-derived endothelial cells express the same transcript for SCF.
Our data suggest that increased release of SCF is a property of hemangioma-derived endothelial cells that may account for the high numbers of mast cells observed in hemangioma tissue. This increased release of SCF is not due to alternate splicing of SCF transcripts by hemangioma cells.
毛细血管瘤是幼儿最常见的肿瘤，由增殖的毛细血管和内皮细胞组成。与周围正常皮肤或组织相比，这些肿瘤还含有大量肥大细胞。我们最近发现，小鼠钢位点的基因产物干细胞因子（SCF）可作为肥大细胞的趋化因子。在本研究中，我们调查了SCF是否可能参与血管瘤中肥大细胞的募集和维持。
将源自小鼠血管瘤的培养内皮细胞与正常血管内皮细胞在产生和释放SCF（一种肥大细胞有丝分裂原）的能力方面进行比较。
血管瘤来源的内皮细胞条件培养基刺激培养的肥大细胞增殖。白细胞介素-3可增强这种增殖活性。相同的条件培养基无法刺激表达缺陷型SCF受体的肥大细胞增殖。当该培养基与针对SCF的中和抗体预孵育时，也无法刺激增殖。对血管瘤细胞和正常内皮细胞条件培养基进行免疫沉淀和蛋白质印迹分析，结果表明仅在血管瘤条件培养基中存在分子量为31,000的SCF。此外，尽管Northern印迹分析表明正常和血管瘤来源的内皮细胞均表达SCF mRNA，但在正常内皮细胞的条件培养基中未显示出对肥大细胞的增殖活性。采用逆转录聚合酶链反应技术扩增编码用于释放SCF的蛋白水解切割位点的DNA序列。结果表明正常和血管瘤来源的内皮细胞表达相同的SCF转录本。
我们的数据表明，SCF释放增加是血管瘤来源内皮细胞的一个特性，这可能解释了在血管瘤组织中观察到的大量肥大细胞。SCF释放的增加并非由于血管瘤细胞对SCF转录本的可变剪接所致。
