Fehlner-Gardiner C C, Uniyal S, von Ballestrem C G, Chan B M
John P. Robarts Research Institute, University of Western Ontario, London, Canada.
Differentiation. 1996 Sep;60(5):317-25. doi: 10.1046/j.1432-0436.1996.6050317.x.
Cytokines have been shown to have major roles in the development of mast cells from bone marrow progenitors. Immature mast cells derived from bone marrow thus leave the blood system to complete their course of maturation within tissues. However, it is now clear that VLA (beta 1) integrins with function in mediating cell-cell and cell-extracellular matrix protein interactions have effects on the growth and differentiation of diverse cell types. At present, the involvement of VLA integrins during mast cell development is still unclear. In this study, we report the preparation of a new monoclonal antibody (mAb) against mouse VLA-5 (alpha 5 beta 1) integrin. Together with mAb R1-2, we characterized the expression of VLA-4 (alpha 4 beta 1) and VLA-5 integrins, the two major fibronectin receptors, on two long-term cultured mast cell lines, CFTL-15 and MC/9. CFTL-15 cells were found to express both VLA-4 and -5 integrins whereas MC/9 cells expressed only VLA-5 but not VLA-4. We speculated that VLA integrin expression may be related to mast cell development. Thus bone marrow-derived mast cells (BMMC) were characterized after varying periods of development induced by IL-3. During the first 3 weeks the expression of VLA-4 and VLA-5 increased progressively and both were involved in mediating adhesion of BMMC to fibronectin. At time periods of greater than 3 weeks, the expression of VLA-4 declined gradually to little, if any, by week 13. In comparison, VLA-5 remained stably expressed and functioned as the major receptor for fibronectin. Results from this study therefore suggest that BMMC differentially utilize VLA-4 and VLA-5 integrins during IL-3-induced development. Differential expression of VLA integrins may have effects on the recirculation properties, tissue distribution and eventual maturation of progenitors to fully matured mast cells.
细胞因子已被证明在骨髓祖细胞发育为肥大细胞的过程中起主要作用。因此，源自骨髓的未成熟肥大细胞离开血液系统，在组织内完成其成熟过程。然而，现在很清楚，具有介导细胞 - 细胞和细胞 - 细胞外基质蛋白相互作用功能的VLA（β1）整合素对多种细胞类型的生长和分化有影响。目前，VLA整合素在肥大细胞发育过程中的作用仍不清楚。在本研究中，我们报告了一种针对小鼠VLA - 5（α5β1）整合素的新型单克隆抗体（mAb）的制备。我们与单克隆抗体R1 - 2一起，对两种长期培养的肥大细胞系CFTL - 15和MC/9上两种主要的纤连蛋白受体VLA - 4（α4β1）和VLA - 5整合素的表达进行了表征。发现CFTL - 15细胞同时表达VLA - 4和 - 5整合素，而MC/9细胞仅表达VLA - 5，不表达VLA - 4。我们推测VLA整合素的表达可能与肥大细胞发育有关。因此，对由IL - 3诱导不同发育时期后的骨髓源性肥大细胞（BMMC）进行了表征。在最初的3周内，VLA - 4和VLA - 5的表达逐渐增加，两者都参与介导BMMC与纤连蛋白的粘附。在大于3周的时间段内，VLA - 4的表达逐渐下降，到第13周时几乎降至零（如果有表达的话）。相比之下，VLA - 5保持稳定表达，并作为纤连蛋白的主要受体发挥作用。因此，本研究结果表明，BMMC在IL - 3诱导的发育过程中差异利用VLA - 4和VLA - 5整合素。VLA整合素的差异表达可能对祖细胞向完全成熟肥大细胞的再循环特性、组织分布和最终成熟产生影响。
