Ra C, Yasuda M, Yagita H, Okumura K
Department of Immunology, Juntendo University, School of Medicine, Tokyo, Japan.
J Allergy Clin Immunol. 1994 Sep;94(3 Pt 2):625-8. doi: 10.1016/0091-6749(94)90139-2.
Mast cells express fibronectin-receptor integrins on the cell surface, which are involved in cellular activation. In this study rat and mouse mast cells adhered to fibronectin through very late antigen 4, 5 (beta 1 integrin) and vitronectin receptor (beta 3 integrin), and engagement of these receptors promoted cellular degranulation induced by cross-linking of the high-affinity IgE receptor. Blocking of these adhesion molecules by monoclonal antibodies remarkably reduced passive cutaneous anaphylaxis reaction in vivo. On fibronectin, cytokine release from mast cells on IgE receptor aggregation was also enhanced, but not the expression of cytokine genes, with the exception of interleukin-3. Interleukin-3 gene expression was constitutively observed in mouse-cultured mast cells and significantly increased on fibronectin with a prolonged survival of the cells, suggesting that the autocrine or paracrine system of interleukin-3 secretion contributes to the prolonged survival of mast cells on fibronectin. Our findings presented here clearly indicate that the engagement of fibronectin-receptor integrins on mast cells increases the sensitivity of the cells for cellular activation. Taking into consideration the fact that mast cells in the microenvironment are actually surrounded by other cells and extracellular matrix proteins, we identified significant roles of adhesion molecules on mast cells in the allergic state, and we hope to develop new strategies to manipulate these molecules for medical intervention in allergy.
肥大细胞在细胞表面表达纤连蛋白受体整合素，这些整合素参与细胞活化。在本研究中，大鼠和小鼠肥大细胞通过极迟抗原4、5（β1整合素）和玻连蛋白受体（β3整合素）黏附于纤连蛋白，这些受体的结合促进了由高亲和力IgE受体交联诱导的细胞脱颗粒。单克隆抗体阻断这些黏附分子可显著降低体内被动皮肤过敏反应。在纤连蛋白上，IgE受体聚集时肥大细胞释放细胞因子也会增强，但细胞因子基因的表达除白细胞介素-3外并未增强。白细胞介素-3基因表达在小鼠培养的肥大细胞中持续存在，且在纤连蛋白上显著增加，细胞存活时间延长，这表明白细胞介素-3分泌的自分泌或旁分泌系统有助于肥大细胞在纤连蛋白上的存活延长。我们在此呈现的研究结果清楚地表明，肥大细胞上纤连蛋白受体整合素的结合增加了细胞对细胞活化的敏感性。考虑到微环境中的肥大细胞实际上被其他细胞和细胞外基质蛋白所包围，我们确定了黏附分子在过敏状态下肥大细胞中的重要作用，并且我们希望开发新的策略来操控这些分子，以便对过敏进行医学干预。
