Erika S Wittchen1, Jaap D van Buul, Keith Burridge, Rebecca A Worthylake. 1. Department of Cell and Developmental Biology, Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7090, USA. erika_wittchen@med.unc.edu
Abstract
PURPOSE OF REVIEW: This review focuses on recent developments in understanding regulation of leukocyte transendothelial migration by small GTPase signaling. RECENT FINDINGS: New studies are refining the model for GTPase regulation of leukocyte-endothelial cell interactions that occur during leukocyte transmigration. An emerging theme is that the endothelial cell is an active participant in this process; an example of this is the identification of a novel leukocyte docking structure. The role of second messengers such as reactive oxygen species downstream and the involvement of kinases such as Pyk2 and Tec kinases upstream of GTPase activation is becoming appreciated. In the leukocyte, finer distinctions between closely related GTPases like Rac1 and Rac2 are being made, and a new role for RhoH has been characterized. Finally, the focus on Rap1 as a key regulator of leukocyte integrin-dependent adhesion is expanding to include roles in endothelial cell-cell adhesion and junctional regulation during transmigration. SUMMARY: Understanding the complex series of events involved in cell-cell interactions during leukocyte transendothelial migration is a prerequisite for designing novel therapies to treat clinical conditions in which an inappropriate inflammatory response leads to disease. A discussion is provided of recent developments in the molecular regulation of leukocyte recruitment.
PURPOSE OF REVIEW: This review focuses on recent developments in understanding regulation of leukocyte transendothelial migration by small GTPase signaling. RECENT FINDINGS: New studies are refining the model for GTPase regulation of leukocyte-endothelial cell interactions that occur during leukocyte transmigration. An emerging theme is that the endothelial cell is an active participant in this process; an example of this is the identification of a novel leukocyte docking structure. The role of second messengers such as reactive oxygen species downstream and the involvement of kinases such as Pyk2 and Tec kinases upstream of GTPase activation is becoming appreciated. In the leukocyte, finer distinctions between closely related GTPases like Rac1 and Rac2 are being made, and a new role for RhoH has been characterized. Finally, the focus on Rap1 as a key regulator of leukocyte integrin-dependent adhesion is expanding to include roles in endothelial cell-cell adhesion and junctional regulation during transmigration. SUMMARY: Understanding the complex series of events involved in cell-cell interactions during leukocyte transendothelial migration is a prerequisite for designing novel therapies to treat clinical conditions in which an inappropriate inflammatory response leads to disease. A discussion is provided of recent developments in the molecular regulation of leukocyte recruitment.
Authors: Nooshin S Bahaie; M Reza Hosseinkhani; Xiao Na Ge; Bit Na Kang; Sung Gil Ha; Malcolm S Blumenthal; Rolf Jessberger; Savita P Rao; P Sriramarao Journal: J Immunol Date: 2011-12-30 Impact factor: 5.422