Slit2 Regulates Attractive Eosinophil and Repulsive Neutrophil Chemotaxis through Differential srGAP1 Expression during Lung Inflammation

	Slit2 Regulates Attractive Eosinophil and Repulsive Neutrophil Chemotaxis through Differential srGAP1 Expression during Lung Inflammation
	Ye, BQ; Geng, ZH; Ma, L; Geng, JG
刊名	JOURNAL OF IMMUNOLOGY
	2010
卷号	185 期号:10 页码:6294-6305
通讯作者	Geng, JG (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, A323 MSRB 3,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA.,jgeng@umich.edu
英文摘要	Directional migration of leukocytes is an essential step in leukocyte trafficking during inflammatory responses. However, the molecular mechanisms governing directional chemotaxis of leukocytes remain poorly understood. The Slit family of guidance cues has been implicated for inhibition of leuocyte migration. We report that Clara cells in the bronchial epithelium secreted Slit2, whereas eosinophils and neutrophils expressed its cell-surface receptor, Robo1. Compared to neutrophils, eosinophils exhibited a significantly lower level of Slit-Robo GTPase-activating protein 1 (srGAP1), leading to activation of Cdc42, recruitment of PI3K to Robo1, enhancment of eotaxin-induced eosinophil chemotaxis, and exaggeration of allergic airway inflammation. Notably, OVA sensitization elicited a Slit2 gradient at so-called bronchus-alveoli axis, with a higher level of Slit2 in the bronchial epithelium and a lower level in the alveolar tissue. Aerosol administration of rSlit2 accelerated eosinophil infiltration, whereas i.v. administered Slit2 reduced eosinophil deposition. In contrast, Slit2 inactivated Cdc42 and suppressed stromal cell-derived factor-1 alpha-induced chemotaxis of neutrophils for inhibiting endotoxin-induced lung inflammation, which were reversed by blockade of srGAP1 binding to Robo1. These results indicate that the newly identified Slit2 gradient at the bronchus-alveoli axis induces attractive PI3K signaling in eosinophils and repulsive srGAP1 signaling in neutrophils through differential srGAP1 expression during lung inflammation. The Journal of Immunology, 2010, 185: 6294-6305.
学科主题	Immunology
类目[WOS]	Immunology
关键词[WOS]	LEUKOCYTE INTEGRIN ACTIVATION ; CELL-MIGRATION ; NEURONAL MIGRATION ; TUMOR ANGIOGENESIS ; AXON GUIDANCE ; P-SELECTIN ; IN-VITRO ; T-CELLS ; KAPPA-B ; ROBO
收录类别	SCI
语种	英语
WOS记录号	WOS:000283848000068
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1053]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Ye, BQ,Geng, ZH,Ma, L,et al. Slit2 Regulates Attractive Eosinophil and Repulsive Neutrophil Chemotaxis through Differential srGAP1 Expression during Lung Inflammation[J]. JOURNAL OF IMMUNOLOGY,2010,185(10):6294-6305.
APA	Ye, BQ,Geng, ZH,Ma, L,&Geng, JG.(2010).Slit2 Regulates Attractive Eosinophil and Repulsive Neutrophil Chemotaxis through Differential srGAP1 Expression during Lung Inflammation.JOURNAL OF IMMUNOLOGY,185(10),6294-6305.
MLA	Ye, BQ,et al."Slit2 Regulates Attractive Eosinophil and Repulsive Neutrophil Chemotaxis through Differential srGAP1 Expression during Lung Inflammation".JOURNAL OF IMMUNOLOGY 185.10(2010):6294-6305.