Heterotropic modulation of selectin affinity by allosteric antibodies affects leukocyte rolling.
J Immunol
; 192(4): 1862-9, 2014 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-24431230
ABSTRACT
Selectins are a family of adhesion receptors designed for efficient leukocyte tethering to the endothelium under shear. As a key property to resist premature bond disruption, selectin adhesiveness is enhanced by tensile forces that promote the conversion of a bent into an extended conformation of the N-terminal lectin and epidermal growth factor-like domains. Conformation-specific Abs have been invaluable in deciphering the activation mechanism of integrins, but similar reagents are not available for selectins. In this study, we show that the anti-human L-selectin mAbs DREG-55 and LAM1-5 but not DREG-56, DREG-200, or LAM1-1 heterotropically modulate adhesion presumably by stabilizing the extended receptor conformation. Force-free affinity assays, flow chamber, and microkinetic studies reveal a ligand-specific modulation of L-selectin affinity by DREG-55 mAb, resulting in a dramatic decrease of rolling velocity under flow. Furthermore, secondary tethering of polymorphonuclear cells was blocked by DREG-200 but significantly boosted by DREG-55 mAb. The results emphasize the need for a new classification for selectin Abs and introduce the new concept of heterotropic modulation of receptor function.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Selectinas
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Migração e Rolagem de Leucócitos
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Anticorpos Monoclonais
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Neutrófilos
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2014
Tipo de documento:
Article