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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); 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.
Source PublicationJOURNAL OF IMMUNOLOGY
2013-04-15
Volume190Issue:8Pages:4371-4381
ISSN0022-1767
AbstractMacrophage-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
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Indexed BySCI
Language英语
WOS IDWOS:000317274500054
Funding OrganizationNational Natural Science Foundation of China [31230027]; National Key Basic Research Foundation of China [2011CB710904]
DepartmentNML分子-细胞生物力学与空间生命科学
Classification二类/Q1
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Document Type期刊论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/47239
Collection国家微重力实验室
Corresponding AuthorLong, 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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