scholarly journals Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration

2008 ◽  
Vol 205 (1) ◽  
pp. 195-205 ◽  
Author(s):  
Nicole A. Morin ◽  
Patrick W. Oakes ◽  
Young-Min Hyun ◽  
Dooyoung Lee ◽  
Y. Eugene Chin ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Myosin Heavy Chain ◽  
T Lymphocyte ◽  
Heavy Chain ◽  
Total Internal Reflection ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Nonmuscle Myosin ◽  
Lymphocyte Migration ◽  
Temporal Regulation

Precise spatial and temporal regulation of cell adhesion and de-adhesion is critical for dynamic lymphocyte migration. Although a great deal of information has been learned about integrin lymphocyte function–associated antigen (LFA)-1 adhesion, the mechanism that regulates efficient LFA-1 de-adhesion from intercellular adhesion molecule (ICAM)-1 during T lymphocyte migration is unknown. Here, we show that nonmuscle myosin heavy chain IIA (MyH9) is recruited to LFA-1 at the uropod of migrating T lymphocytes, and inhibition of the association of MyH9 with LFA-1 results in extreme uropod elongation, defective tail detachment, and decreased lymphocyte migration on ICAM-1, without affecting LFA-1 activation by chemokine CXCL-12. This defect was reversed by a small molecule antagonist that inhibits both LFA-1 affinity and avidity regulation, but not by an antagonist that inhibits only affinity regulation. Total internal reflection fluorescence microscopy of the contact zone between migrating T lymphocytes and ICAM-1 substrate revealed that inactive LFA-1 is selectively localized to the posterior of polarized T lymphocytes, whereas active LFA-1 is localized to their anterior. Thus, during T lymphocyte migration, uropodal adhesion depends on LFA-1 avidity, where MyH9 serves as a key mechanical link between LFA-1 and the cytoskeleton that is critical for LFA-1 de-adhesion.

The integrin LFA-1 signals through ZAP-70 to regulate expression of high-affinity LFA-1 on T lymphocytes

Blood ◽  
2011 ◽  
Vol 117 (12) ◽  
pp. 3331-3342 ◽  
Author(s):  
Rachel Evans ◽  
Annemarie C. Lellouch ◽  
Lena Svensson ◽  
Alison McDowall ◽  
Nancy Hogg
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Tyrosine Kinases ◽  
Close Contact ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Lymphocyte Migration ◽  
High Affinity ◽  
And Migration

Abstract The integrin lymphocyte function-associated antigen 1 (LFA-1) controls many functions of T lymphocytes and is particularly essential during lymphocyte migration from blood into tissues. LFA-1 is considered to initiate “outside-in” signaling when bound to ligand intercellular adhesion molecule 1 (ICAM-1), but little is known about the proteins involved or where in the cell such LFA-1–mediated signaling might be operating. Here we show that LFA-1 is constitutively associated with the protein tyrosine kinases Lck and zeta chain–associated protein of 70 kDa (ZAP-70). When LFA-1 binds ICAM-1, both kinases become phosphorylated and the consequence of kinase activation is the conversion of intermediate- to high-affinity LFA-1 and an increase in close contact with ICAM-1. In the polarized T lymphocyte, phospho-ZAP-70 is concentrated within a region of high-affinity LFA-1 that includes talin and encompasses the lamella/lamellipodial interface as well as further back in the cell. Deficiency of ZAP-70 through inhibition or knockdown in T lymphocytes decreases the speed of migration on ICAM-1, as well as reducing firm adhesion under shear-flow conditions. Through its control of high-affinity LFA-1, the LFA-1/Lck/ZAP-70 complex is in position to initiate the rapid adhesion strengthening and migration necessary for T-lymphocyte responses when stimulated vasculature is encountered at sites of infection or injury.

scholarly journals Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration

2008 ◽  
Vol 180 (2) ◽  
pp. i5-i5
Author(s):  
Nicole A. Morin ◽  
Patrick W. Oakes ◽  
Young-Min Hyun ◽  
Dooyoung Lee ◽  
Eugene Y. Chin ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
T Lymphocyte ◽  
Heavy Chain ◽  
Nonmuscle Myosin ◽  
Lymphocyte Migration

scholarly journals Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration

2008 ◽  
Vol 205 (4) ◽  
pp. 993-993
Author(s):  
Nicole A. Morin ◽  
Patrick W. Oakes ◽  
Young-Min Hyun ◽  
Dooyoung Lee ◽  
Y. Eugene Chin ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
T Lymphocyte ◽  
Heavy Chain ◽  
Nonmuscle Myosin ◽  
Lymphocyte Migration

scholarly journals Cutting Edge: Association of the Motor Protein Nonmuscle Myosin Heavy Chain-IIA with the C Terminus of the Chemokine Receptor CXCR4 in T Lymphocytes

2002 ◽  
Vol 169 (10) ◽  
pp. 5410-5414 ◽  
Author(s):  
Mercedes Rey ◽  
Miguel Vicente-Manzanares ◽  
Fernando Viedma ◽  
María Yáñez-Mó ◽  
Ana Urzainqui ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Chemokine Receptor ◽  
Motor Protein ◽  
Cutting Edge ◽  
Nonmuscle Myosin ◽  
Chemokine Receptor Cxcr4 ◽  
C Terminus

B2 exon splicing of nonmuscle myosin heavy chain IIB is differently regulated in developing and adult rat brain

2000 ◽  
Vol 37 (4) ◽  
pp. 299-306 ◽  
Author(s):  
Taisuke Miyazaki ◽  
Masahiko Watanabe ◽  
Akihiko Yamagishi ◽  
Masayuki Takahashi
Keyword(s):  
Myosin Heavy Chain ◽  
Rat Brain ◽  
Heavy Chain ◽  
Nonmuscle Myosin ◽  
Adult Rat ◽  
Exon Splicing ◽  
Adult Rat Brain

scholarly journals Immune Checkpoint Receptors Tim-3 and PD-1 Regulate Monocyte and T Lymphocyte Function in Septic Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Qi Xia ◽  
Li Wei ◽  
Yuntao Zhang ◽  
Jifang Sheng ◽  
Wei Wu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
T Lymphocytes ◽  
Signaling Pathway ◽  
T Lymphocyte ◽  
Receptor Blockade ◽  
Lymphocyte Function ◽  
Significant Elevation ◽  
Programmed Cell Death 1 ◽  
Checkpoint Receptors

We aim to investigate the effects of Tim-3 and programmed cell death-1 (PD-1) on the monocytes and T lymphocytes in septic patients. Expression of Tim-3 and PD-1 on the CD3, CD4, and CD8 lymphocytes and monocytes was determined using flow cytometry. CBA technique was utilized to determine the expression of cytokines in the lymphocyte supernatant in addition to the IL-10 and TNF-αpositivity in monocytes in the presence of Tim-3 and/or PD-1 receptor blockade. Compared with the normal control, significant elevation was observed in the expression of PD-1 on CD3 (P=0.004), CD4, and CD8 monocytes. Blockade of the Tim-3 signaling pathway contributed to the significant elevation of IL-10 and TNF-αin the supernatant of T lymphocytes in the septic patients, while the PD-1 signaling pathway blockade only triggered the obvious elevation of TNF-αin the T lymphocytes. Blockade of Tim-3 and PD-1 induced the positivity of IL-10- and TNF-α-expressing cells in the peripheral monocytes. Significant changes were noticed in the Tim-3 and PD-1 in the T lymphocytes and monocytes. Blockade of Tim-3 and PD-1 contributed to the function of lymphocytes and monocytes. In the septic process, Tim-3 and PD-1 played crucial roles in the immune response of T lymphocytes and monocytes.

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