Cell surface tissue transglutaminase is involved in adhesion and migration of monocytic cells on fibronectin
Cell surface tissue transglutaminase is involved in adhesion and migration of monocytic cells on fibronectin
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DOI：
10.1182/blood.v98.5.1567
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发表时间：
2001-09-01
期刊：
影响因子：
20.3
通讯作者：
Belkin, AM
中科院分区：
文献类型：
--
作者：
Akimov, SS;Belkin, AM
在单核细胞向巨噬细胞分化的过程中，组织转谷氨酰胺酶（transglutaminase II, tTG）的表达急剧增加；然而，它在单核细胞中的作用在很大程度上仍然未知。本研究描述了细胞表面tTG作为纤维连接蛋白（Fn）的粘附和迁移受体的新功能。两种结构相关的转谷氨酰胺酶tTG和因子XIII的A亚基（FXIIIA）在单核细胞表面表达，而只有表面tTG与β(1)和β(3)亚家族的多个整合素相关。在单核细胞向巨噬细胞转化的过程中，tTG的表面水平和整合素结合的tTG的量都急剧上调。相反，FXIIIA的生物合成和表面表达的减少伴随着单核细胞分化。细胞表面tTG与β(1)-和β(3)-整合素共定位于巨噬细胞附着在Fn上的囊体样粘附结构中。通过表达反义tTG构建体或通过功能阻断抗体抑制表面tTG，可显著降低单核细胞在Fn上的粘附和扩散，特别是在由模块i6i1,2i7 -9组成的Fn明胶结合片段上。同样，干扰tTG表面的粘附功能可显著减少髓细胞在Fn及其明胶结合片段上的迁移。这些数据表明，细胞表面tTG作为一种整合素相关的粘附受体，可能参与单核细胞在炎症期间向含有Fn基质的组织的外渗和迁移。(C) 2001年由美国血液学会出版。
Expression of tissue transglutaminase (transglutaminase II, tTG) was shown to increase drastically during monocyte differentiation into macrophages; however, its role in monocytic cells remains largely unknown. This study describes a novel function of cell surface tTG as an adhesion and migration receptor for fibronectin (Fn). Two structurally related transglutaminases, tTG and the A subunit of factor XIII (FXIIIA), are expressed on the surface of monocytic cells, whereas only surface tTG is associated with multiple Integrins of the beta (1) and beta (3) subfamilies. Both surface levels of tTG and the amounts of integrin-bound tTG are sharply up-regulated during the conversion of monocytes into macrophages. In contrast, a reduction in biosynthesis and surface expression of FXIIIA accompanies monocyte differentiation. Cell surface tTG is colocalized with beta (1)- and beta (3)-integrins in podosomelike adhesive structures of macrophages adherent on Fn. Down-regulation of surface tTG by expression of antisense tTG construct or its inhibition by function-blocking antibodies significantly decreases adhesion and spreading of monocytic cells on Fn and, in particular, on the gelatin-binding fragment of Fn consisting of modules I6II1,2I7-9. Likewise, interfering with the adhesive function of surface tTG markedly reduces migration of myeloid cells on Fn and its gelatin-binding fragment. These data demonstrate that cell surface tTG serves as an integrin-associated adhesion receptor that might be involved in extravasation and migration of monocytic cells into tissues containing Fn matrices during inflammation. (C) 2001 by The American Society of Hematology.