Distinct binding affinities of Mac-1 and LFA-1 in neutrophil activation

	Distinct binding affinities of Mac-1 and LFA-1 in neutrophil activation
	Li N(李宁); Mao DB(毛德斌); Lv SQ(吕守芹); Tong CF(佟春芳); Zhang Y(章燕); Long M(龙勉)
刊名	JOURNAL OF IMMUNOLOGY
	2013-04-15
通讯作者邮箱	mlong@imech.ac.cn
卷号	190 期号:8 页码:4371-4381
ISSN号	0022-1767
通讯作者	Long, M (reprint author), Chinese Acad Sci, Inst Mech, Natl Micrograv Lab, Key Lab Micrograv, 15 North 4th Ring Rd, Beijing 100190, Peoples R China.
产权排序	[Li, Ning; Mao, Debin; Lu, Shouqin; Tong, Chunfang; Zhang, Yan; Long, Mian] Chinese Acad Sci, Inst Mech, Natl Micrograv Lab, Key Lab Micrograv, Beijing 100190, Peoples R China; [Li, Ning; Mao, Debin; Lu, Shouqin; Tong, Chunfang; Zhang, Yan; Long, Mian] Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing 100190, Peoples R China
中文摘要	Macrophage-1 Ag (Mac-1) and lymphocyte function-associated Ag-1 (LFA-1), two beta(2) integrins expressed on neutrophils (PMNs), mediate PMN recruitment cascade by binding to intercellular adhesive molecule 1. Distinct functions of LFA-1-initiating PMN slow rolling and firm adhesion but Mac-1-mediating cell crawling are assumed to be governed by the differences in their binding affinities and kinetic rates. In this study, we applied an adhesion frequency approach to compare their kinetics in the quiescent and activated states using three molecular systems, constitutively expressed receptors on PMNs, wild-type and high-affinity (HA) full-length constructs transfected on 293T cells, and wild-type and HA recombinant extracellular constructs. Data indicate that the difference in binding affinity between Mac-1 and LFA-1 is on-rate dominated with slightly or moderately varied off-rate. This finding was further confirmed when both beta(2) integrins were activated by chemokines (fMLF or IL-8), divalent cations (Mg2+ or Mn2+), or disulfide bond lockage on an HA state. Structural analyses reveal that such the kinetics difference is likely attributed to the distinct conformations at the interface of Mac-1 or LFA-1 and intercellular adhesive molecule 1. This work furthers the understandings in the kinetic differences between Mac-1 and LFA-1 and in their biological correlations with molecular activation and structural bases. The Journal of Immunology, 2013, 190: 4371-4381.
学科主题	生物力学
分类号	二类/Q1
收录类别	SCI
资助信息	National Natural Science Foundation of China [31230027]; National Key Basic Research Foundation of China [2011CB710904]
原文出处	http://dx.doi.org/10.4049/jimmunol.1201374
语种	英语
WOS记录号	WOS:000317274500054
公开日期	2013-05-21
内容类型	期刊论文
源URL	[http://dspace.imech.ac.cn/handle/311007/47239]
专题	力学研究所_国家微重力实验室
推荐引用方式 GB/T 7714	Li N,Mao DB,Lv SQ,et al. Distinct binding affinities of Mac-1 and LFA-1 in neutrophil activation[J]. JOURNAL OF IMMUNOLOGY,2013,190(8):4371-4381.
APA	Li N,Mao DB,Lv SQ,Tong CF,Zhang Y,&Long M.(2013).Distinct binding affinities of Mac-1 and LFA-1 in neutrophil activation.JOURNAL OF IMMUNOLOGY,190(8),4371-4381.
MLA	Li N,et al."Distinct binding affinities of Mac-1 and LFA-1 in neutrophil activation".JOURNAL OF IMMUNOLOGY 190.8(2013):4371-4381.