Expression and function of alpha 4/beta 7 integrin on human natural killer cells.
In this report we have analysed the expression and function of the alpha 4/beta 7 heterodimer in human natural killer (NK) cells. The expression of alpha 4 beta 7 is induced in NK cells upon activation as the anti alpha 4 beta 2 ACT-1 monoclonal antibody (mAb) family 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 on its F(ab) fragments induced a strong homotypic adhesion of NK cells, comparable to than stimulated by the anti-alpha 4 HPI 7 mAb. Cell cell interaction induced by the ACT-1 mAb was only prevented by another anti-alpha 4 mAb (HP2.1) that recognizes a different epitope. In alpha 4 beta 7-mediated cell aggregation the alpha 4 beta 7 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 alpha 4 beta 7 and alpha 4 beta 7 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-beta 7 mAb LIAI 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 alpha 4 beta 7 binding sites for both ligands appear to be different. Our results indicate that upon IL-2-activation, expression of functional alpha 4 beta-integrin is induced on NK cells potentially participating in their interaction with both extracellular matrix and endothelial cells.
Servn to de Immunologia Hospital de la Prineesa, Madrid, Spain.
J J
JJ
Pérez-Villar
J M
JM
Zapata
I
I
Melero
A
A
Postigo
E
E
Sánchez-Madrid
M
M
López-Botet
D002448:Cell Adhesion; D002449:Cell Aggregation; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D008213:Lymphocyte Activation; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D016029:Receptors, Very Late Antigen / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D007376:Interleukin-2; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; C071777:integrin alpha4beta7