LFA-1 integrin antibodies inhibit leukocyte α4ß1-mediated adhesion by intracellular signaling.
Blood
; 128(9): 1270-81, 2016 09 01.
Article
em En
| MEDLINE
| ID: mdl-27443292
ABSTRACT
Binding of intercellular adhesion molecule-1 to the ß2-integrin leukocyte function associated antigen-1 (LFA-1) is known to induce cross-talk to the α4ß1 integrin. Using different LFA-1 monoclonal antibodies, we have been able to study the requirement and mechanism of action for the cross-talk in considerable detail. LFA-1-activating antibodies and those inhibitory antibodies that signal to α4ß1 induce phosphorylation of Thr-758 on the ß2-chain, which is followed by binding of 14-3-3 proteins and signaling through the G protein exchange factor Tiam1. This results in dephosphorylation of Thr-788/789 on the ß1-chain of α4ß1 and loss of binding to its ligand vascular cell adhesion molecule-1. The results show that with LFA-1 antibodies, we can activate LFA-1 and inhibit α4ß1, inhibit both LFA-1 and α4ß1, inhibit LFA-1 but not α4ß1, or not affect LFA-1 or α4ß1 These findings are important for the understanding of integrin regulation and for the interpretation of the effect of integrin antibodies and their use in clinical applications.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Antígeno-1 Associado à Função Linfocitária
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Integrina alfa4beta1
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Leucócitos
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Anticorpos
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article