Lipid Raft is required for PSGL-1 ligation induced HL-60 cell adhesion on ICAM-1.

P-selectin glycoprotein ligand-1 (PSGL-1) and integrins are adhesion molecules that play critical roles in host defense and innate immunity. PSGL-1 mediates leukocyte rolling and primes leukocytes for integrin-mediated adhesion. However, the mechanism that PSGL-1 as a rolling receptor in regulating...

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Main Authors: Tingshuang Xu, Wenai Liu, Jixian Luo, Chunfeng Li, Xueqing Ba, Khamal Kwesi Ampah, Xiaoguang Wang, Yong Jiang, Xianlu Zeng
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3849276?pdf=render
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author Tingshuang Xu
Wenai Liu
Jixian Luo
Chunfeng Li
Xueqing Ba
Khamal Kwesi Ampah
Xiaoguang Wang
Yong Jiang
Xianlu Zeng
author_facet Tingshuang Xu
Wenai Liu
Jixian Luo
Chunfeng Li
Xueqing Ba
Khamal Kwesi Ampah
Xiaoguang Wang
Yong Jiang
Xianlu Zeng
author_sort Tingshuang Xu
collection DOAJ
description P-selectin glycoprotein ligand-1 (PSGL-1) and integrins are adhesion molecules that play critical roles in host defense and innate immunity. PSGL-1 mediates leukocyte rolling and primes leukocytes for integrin-mediated adhesion. However, the mechanism that PSGL-1 as a rolling receptor in regulating integrin activation has not been well characterized. Here, we investigate the function of lipid raft in regulating PSGL-1 induced β2 integrin-mediated HL-60 cells adhesion. PSGL-1 ligation with antibody enhances the β2 integrin activation and β2 integrin-dependent adhesion to ICAM-1. Importantly, with the treatment of methyl-β-cyclodextrin (MβCD), we confirm the role of lipid raft in regulating the activation of β2 integrin. Furthermore, we find that the protein level of PSGL-1 decreased in raft fractions in MβCD treated cells. PSGL-1 ligation induces the recruitment of spleen tyrosine kinase (Syk), a tyrosine kinase and Vav1 (the pivotal downstream effector of Syk signaling pathway involved in cytoskeleton regulation) to lipid raft. Inhibition of Syk activity with pharmacologic inhibitor strongly reduces HL-60 cells adhesion, implicating Syk is crucial for PSGL-1 mediated β2 integrin activation. Taken together, we report that ligation of PSGL-1 on HL-60 cells activates β2 integrin, for which lipid raft integrity and Syk activation are responsible. These findings have shed new light on the mechanisms that connect leukocyte initial rolling with subsequent adhesion.
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spelling doaj.art-358d0ac200d34a37842994803ecaf3622022-12-22T03:11:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8180710.1371/journal.pone.0081807Lipid Raft is required for PSGL-1 ligation induced HL-60 cell adhesion on ICAM-1.Tingshuang XuWenai LiuJixian LuoChunfeng LiXueqing BaKhamal Kwesi AmpahXiaoguang WangYong JiangXianlu ZengP-selectin glycoprotein ligand-1 (PSGL-1) and integrins are adhesion molecules that play critical roles in host defense and innate immunity. PSGL-1 mediates leukocyte rolling and primes leukocytes for integrin-mediated adhesion. However, the mechanism that PSGL-1 as a rolling receptor in regulating integrin activation has not been well characterized. Here, we investigate the function of lipid raft in regulating PSGL-1 induced β2 integrin-mediated HL-60 cells adhesion. PSGL-1 ligation with antibody enhances the β2 integrin activation and β2 integrin-dependent adhesion to ICAM-1. Importantly, with the treatment of methyl-β-cyclodextrin (MβCD), we confirm the role of lipid raft in regulating the activation of β2 integrin. Furthermore, we find that the protein level of PSGL-1 decreased in raft fractions in MβCD treated cells. PSGL-1 ligation induces the recruitment of spleen tyrosine kinase (Syk), a tyrosine kinase and Vav1 (the pivotal downstream effector of Syk signaling pathway involved in cytoskeleton regulation) to lipid raft. Inhibition of Syk activity with pharmacologic inhibitor strongly reduces HL-60 cells adhesion, implicating Syk is crucial for PSGL-1 mediated β2 integrin activation. Taken together, we report that ligation of PSGL-1 on HL-60 cells activates β2 integrin, for which lipid raft integrity and Syk activation are responsible. These findings have shed new light on the mechanisms that connect leukocyte initial rolling with subsequent adhesion.http://europepmc.org/articles/PMC3849276?pdf=render
spellingShingle Tingshuang Xu
Wenai Liu
Jixian Luo
Chunfeng Li
Xueqing Ba
Khamal Kwesi Ampah
Xiaoguang Wang
Yong Jiang
Xianlu Zeng
Lipid Raft is required for PSGL-1 ligation induced HL-60 cell adhesion on ICAM-1.
PLoS ONE
title Lipid Raft is required for PSGL-1 ligation induced HL-60 cell adhesion on ICAM-1.
title_full Lipid Raft is required for PSGL-1 ligation induced HL-60 cell adhesion on ICAM-1.
title_fullStr Lipid Raft is required for PSGL-1 ligation induced HL-60 cell adhesion on ICAM-1.
title_full_unstemmed Lipid Raft is required for PSGL-1 ligation induced HL-60 cell adhesion on ICAM-1.
title_short Lipid Raft is required for PSGL-1 ligation induced HL-60 cell adhesion on ICAM-1.
title_sort lipid raft is required for psgl 1 ligation induced hl 60 cell adhesion on icam 1
url http://europepmc.org/articles/PMC3849276?pdf=render
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AT wenailiu lipidraftisrequiredforpsgl1ligationinducedhl60celladhesiononicam1
AT jixianluo lipidraftisrequiredforpsgl1ligationinducedhl60celladhesiononicam1
AT chunfengli lipidraftisrequiredforpsgl1ligationinducedhl60celladhesiononicam1
AT xueqingba lipidraftisrequiredforpsgl1ligationinducedhl60celladhesiononicam1
AT khamalkwesiampah lipidraftisrequiredforpsgl1ligationinducedhl60celladhesiononicam1
AT xiaoguangwang lipidraftisrequiredforpsgl1ligationinducedhl60celladhesiononicam1
AT yongjiang lipidraftisrequiredforpsgl1ligationinducedhl60celladhesiononicam1
AT xianluzeng lipidraftisrequiredforpsgl1ligationinducedhl60celladhesiononicam1