Expression and function of α4/β7 integrin on human natural killer cells
In this report, we have analysed the expression and function of the α4/β7 heterodimer in human natural killer (NK) cells. The expression of α4β7 is induced in NK cells upon activation, as the anti-α4β7 ACT-1 monoclonal antibody (mAb) faintly stained a minority of peripheral blood NK cells, whereas it strongly reacted with in vitro long-term interleukin-2 (IL-2)-activated NK cells. Incubation with ACT-1 or its F(ab′)2 fragments induced a strong homotypic adhesion of NK cells, comparable to that stimulated by the anti-α4 HP1/7 mAb. Cell–cell interaction induced by the ACT-1 mAb was only prevented by another anti-α4 mAb (HP2/1) that recognizes a different epitope. In α4β7-mediated cell aggregation, the α4β7 heterodimer was redistributed to intercellular contact sites, thus, suggesting a direct involvement of this integrin in the formation of cell clusters. In NK cells attached to Fibronectin (FN38) or vascular cell adhesion molecule-1 (VCAM-1), both α4β7 and α4β1 integrins were redistributed at the ventral cellular membrane forming discrete contact sites. The ACT-1 mAb only partially blocked NK cell binding to FN38, but in combination with the anti-β1 mAb LIA1/2, NK cell binding to FN38 was completely inhibited. In contrast, ACT-1 did not modify NK cell adhesion to VCAM-1, thus supporting the theory that the α4β7 binding sites for both ligands appear to be different. Our results indicate that upon IL-2-activation, expression of functional α4/β7 integrin is induced on NK cells, potentially participating in their interaction with both extracellular matrix and endothelial cells.
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Document Type: Research Article
Affiliations: Servicio de Inmunología Hospital de la Princesa, Madrid, Spain
Publication date: September 1, 1996