MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes

被引:285
作者
Vogl, T
Ludwig, S
Goebeler, M
Strey, A
Thorey, IS
Reichelt, R
Foell, D
Gerke, V
Manitz, MP
Nacken, W
Werner, S
Sorg, C
Roth, J
机构
[1] Univ Munster, Inst Expt Dermatol, Dept Pediat, D-48149 Munster, Germany
[2] Univ Munster, Inst Mol Virol, D-48149 Munster, Germany
[3] Univ Wurzburg, Dept Dermatol, D-97070 Wurzburg, Germany
[4] Univ Munster, Inst Med Biochem, D-48149 Munster, Germany
[5] ETH, Inst Cell Biol, CH-8093 Zurich, Switzerland
[6] Univ Munster, Inst Med Phys, Dept Pediat, D-48149 Munster, Germany
关键词
D O I
10.1182/blood-2004-02-0446
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
MRP14 (S100A9) is the major calcium-binding protein of neutrophils and monocytes. Targeted gene disruption reveals an essential role of this S100 protein for transendothelial migration of phagocytes. The underlying molecular mechanism comprises major alterations of cytoskeletal metabolism. MRP14, in complex with its binding partner MRP8 (S100A8), promotes polymerization of microtubules. MRP14 is specifically phosphorylated by p38 mitogen-activated protein kinase (MAPK). This phosphorylation inhibits MRPB/MRP14-induced tubulin polymerization. Phosphorylation of MRP14 is antagonistically regulated by binding of MRP8 and calcium. The biologic relevance of these findings is confirmed by the fact that MAPK p38 fails to stimulate migration of MRP14(-/-) granulocytes in vitro and MRP14(-/-) mice show a diminished recruitment of granulocytes into the granulation tissue during wound healing in vivo. MRP14(-/-) granulocytes contain significantly less polymerized tubulin, which subsequently results in minor activation of Rac1 and Cdc42 after stimulation of p38 MAPK. Thus, the complex of MRP8/MRP14 is the first characterized molecular target integrating MAPK- and calcium-dependent signals during migration of phagocytes. (C) 2004 by The American Society of Hematology.
引用
收藏
页码:4260 / 4268
页数:9
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