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Impact of real-time shedding on binding kinetics of membrane-remaining L-selectin to PSGL-1
Peng S(彭爽); Chen SB(陈深宝); Li LD(李林达); Tong CF(佟春芳); Li N(李宁); Lv SQ(吕守芹); Long M(龙勉)
Corresponding AuthorLong, Mian(mlongi@imech.ac.cn)
Source PublicationAMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
2019-05-01
Volume316Issue:5Pages:C678-C689
ISSN0363-6143
AbstractL-selectin shedding induced by various cytokines is crucial in activating neutrophils (PMNs) in inflammatory cascade. While the real-time shedding in vivo lasts similar to 10 min after PMN activation, the impact of time-dependent shedding on binding kinetics of membrane-remaining L-selectins to its ligands is poorly understood at transient or steady state. Ilere, we developed an in vitro L-selectin shedding dynamics approach. together with competitive assays of cell adhesion, and proposed a theoretical model for quantifying the impact of real-time shedding on the binding kinetics of membrane-remaining L-selectins to P-selectin glycoprotein ligand-1 (PSGL-1). Our data indicated that the extent of L-selectin shedding on PMA activation is higher, but the terminating time is longer for Jurkat cells than those for human PMNs. Meanwhile, fMLF or IL-8 stimulation yields the longer terminating time than that on PMA stimulation but results in a similar shedding extent for PMNs. L-selectin shedding reduces L-selectin-PSGL-1-mediated cell adhesion in three ways: decreasing membrane-anchored L-selectins, increasing soluble L-selectins competitively binding to ligands, and presenting conformational alteration of membrane-remaining L-selectins themselves. Compared with those on intact cells, the binding affinities of membrane-remaining L-selectin-PSOL-1 pairs were all enhanced at initial and lowered at the late shedding phase for both PMN and Jurkat cells even with varied transition time points. The rolling velocities of both PMNs and Jurkat cells were increased following mechanically or biochemically induced shedding of L-selectin under shear flow. These findings help to further our understanding of the function of time-dependent L-selectin shedding during the inflammation cascade.
Keywordbinding kinetics competitive binding L-selectin modeling real-time shedding
DOI10.1152/ajpcell.00212.2018
Indexed BySCI
Language英语
WOS IDWOS:000467994300004
WOS KeywordRECEPTOR-LIGAND INTERACTIONS ; GLYCOPROTEIN LIGAND-1 ; P-SELECTIN ; 2-DIMENSIONAL KINETICS ; SURFACE ; BETA(2)-INTEGRIN ; INFLAMMATION ; NEUTROPHILS ; INHIBITION ; CLEAVAGE
WOS Research AreaCell Biology ; Physiology
WOS SubjectCell Biology ; Physiology
Funding ProjectNational Key Research and Development Program of China[2016YFA0501601] ; National Natural Science Foundation of China[91642203] ; National Natural Science Foundation of China[31570942] ; National Natural Science Foundation of China[31230027] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDB22040101] ; Frontier Science Key Project of Chinese Science Academy[QYZDJ-SSW-JSC018]
Funding OrganizationNational Key Research and Development Program of China ; National Natural Science Foundation of China ; Strategic Priority Research Program of Chinese Academy of Sciences ; Frontier Science Key Project of Chinese Science Academy
Classification二类
Ranking1
ContributorLong, Mian
Citation statistics
Document Type期刊论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/80720
Collection国家微重力实验室
Recommended Citation
GB/T 7714
Peng S,Chen SB,Li LD,et al. Impact of real-time shedding on binding kinetics of membrane-remaining L-selectin to PSGL-1[J]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY,2019,316(5):C678-C689.
APA 彭爽.,陈深宝.,李林达.,佟春芳.,李宁.,...&龙勉.(2019).Impact of real-time shedding on binding kinetics of membrane-remaining L-selectin to PSGL-1.AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY,316(5),C678-C689.
MLA 彭爽,et al."Impact of real-time shedding on binding kinetics of membrane-remaining L-selectin to PSGL-1".AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 316.5(2019):C678-C689.
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