RhoH is required to maintain the integrin LFA-1 in a nonadhesive state on lymphocytes

Speaker：蔡明怡

Commentator：楊倍昌 老師

Time：15:00-16:00 10/13/2004

Place：Room 601

Abstract

    Lymphocyte function associated antigen 1 （LFA-1） is expressed on all leukocytes and it play an important role in leukocyte migration, antigen presentation and cellular cytotoxicity by binding to its cellular ligands（e.g. ICAM-1,ICAM-2 and ICAM-3）. On the resting cells, LFA-1 is in a nonadhesive state. When the cells are activated by a variety of stimuli, LFA-1 change to a adhesive state. Based on the previous studies, some small GTPases and Rho family GTPases can affect the LFA-1 mediated adhesion. For example, over expression of Rap1-specific GTPase-actvating protein, SPA-1, or inactivated form of Rap-1, blocked PMA triggered LFA-1 mediated adhesion to ICAM-1¹. RhoA kinase activation is required for leukocyte de-adhesion². But how the lymphocytes maintain the LFA-1 in a nonadhesive state when it is resting is still poorly understood? The authors used retovirus which inserted in RHOH and generated a Jurkat T cell clone, J﹢hi 1.4 in this study. They found that J﹢hi 1.4 contain low amounts of mRNA for RhoH, and expressed constitutively adhesive LFA-1. The J﹢hi 1.4 bound to ICAM-1,ICAM-2 and ICAM-3 spontaneously, but the constitutively adhesion phenotype of J﹢hi 1.4 will be reverted to that of wile-type by reconstitution of RhoH mRNA expression. Finally, they using RhoH RNAi in peripheral blood lymphocyte and found similar results with the data showed previously. The authors demonstrate that RhoH is a important element of the resting lymphocyte to maintain LFA-1 in a low adhesive state.

References：

1.     Liu L. et al. The GTPase Rap1 regulates phorbol 12-myristate 13 –acetate-stimulated but not ligand-induced β1 integrin-dependent leukocyte adhesion. J. Biol. Chem. 277, 40893-40900（2002）

2.     Liu L. et al. Requirement for Rho A kinase activation in leukocyte de-adhesion. J. Immunol. 169, 2330-2336（2002）.