Non-canonical PI3K-Cdc42-Pak-Mek-Erk Signaling Promotes Immune-Complex-Induced Apoptosis in Human Neutrophils

被引：30

作者：

Chu, Julia Y. ^{[1
]}

Dransfield, Ian ^{[1
]}

Rossi, Adriano G. ^{[1
]}

Vermeren, Sonja ^{[1
]}

机构：

[1] Univ Edinburgh, Queens Med Res Inst, MRC, Ctr Inflammat Res, 47 Little France Crescent, Edinburgh EH16 4TJ, Midlothian, Scotland

来源：

CELL REPORTS | 2016年 / 17卷 / 02期

基金：

英国医学研究理事会;

关键词：

NUCLEOTIDE EXCHANGE FACTOR; CROSS-CASCADE ACTIVATION; PROTEIN-KINASE B; BONE-MARROW; GROWTH-FACTOR; MECHANISMS; ERK; INHIBITORS; PATHWAY; MEK1;

D O I：

10.1016/j.celrep.2016.09.006

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Neutrophils are peripheral blood leukocytes that represent the first line of immune cell defense against bacterial and fungal infections but are also crucial players in the generation of the inflammatory response. Many neutrophil cell surface receptors regulate important cellular processes via activation of agonist-activated PI3Ks. We show here that activation of human neutrophils with insoluble immune complexes drives a previously uncharacterized, PI3K-dependent, non-canonical, pro-apoptotic signaling pathway, Fc gamma R-PI3K beta/delta-Cdc42-Pak-Mek-Erk. This is a rare demonstration of Ras/Raf-independent activation of Erk and of PI3K-mediated activation of Cdc42. In addition, comparative analysis of immune-complex- and fMLF-induced signaling uncovers key differences in pathways used by human and murine neutrophils. The non-canonical pathway we identify in this study may be important for the resolution of inflammation in chronic inflammatory diseases that rely on immune-complex-driven neutrophil activation.

引用

页码：374 / 386

页数：13

共 60 条

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