Heterotropic Modulation of Selectin Affinity by Allosteric Antibodies Affects Leukocyte Rolling
Autor: | Rupert Hallmann, Sebastian B. Riese, Konrad Buscher, Christian Kuehne, Thomas F. Tedder, Erhard Hohenester |
---|---|
Rok vydání: | 2014 |
Předmět: |
Neutrophils
Immunology Allosteric regulation Integrin Leukocyte Rolling Jurkat cells Antibodies Article Cell Line Jurkat Cells Cell Adhesion Humans Immunology and Allergy Amino Acid Sequence Receptor biology Chemistry Antibodies Monoclonal Lectin Adhesion Biochemistry Selectins Biophysics biology.protein Sequence Alignment Selectin |
Zdroj: | The Journal of Immunology. 192:1862-1869 |
ISSN: | 1550-6606 0022-1767 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |