Distinct binding affinities of Mac-1 and LFA-1 in neutrophil activation | |
Li N(李宁)![]() ![]() ![]() ![]() ![]() | |
Source Publication | JOURNAL OF IMMUNOLOGY
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2013-04-15 | |
Volume | 190Issue:8Pages:4371-4381 |
ISSN | 0022-1767 |
Abstract | 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. |
Subject Area | 生物力学 |
URL | 查看原文 |
Indexed By | SCI |
Language | 英语 |
WOS ID | WOS:000317274500054 |
Funding Organization | National Natural Science Foundation of China [31230027]; National Key Basic Research Foundation of China [2011CB710904] |
Department | NML分子-细胞生物力学与空间生命科学 |
Classification | 二类/Q1 |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://dspace.imech.ac.cn/handle/311007/47239 |
Collection | 微重力重点实验室 |
Corresponding Author | 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. |
Recommended Citation 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. |
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