ICAM-2 redistributed by ezrin as a target for killer cells.
Very little is known about the receptors and target molecules involved in natural killer (NK) cell activity. Here we present a model system in which interleukin-2-activated killing by NK cells depends on the intercellular adhesion molecule ICAM-2 and is regulated by the distribution of ICAM-2. The level of ICAM-2 expression in NK-sensitive and resistant cells is similar, but in sensitive cells ICAM-2 is concentrated into bud-like cellular projections known as uropods, whereas in resistant cells it is evenly distributed. The cytoskeletal-membrane linker protein ezrin is also localized in uropods. Transfection of human ezrin into NK-resistant cells induces uropods formation, redistribution of ICAM-2 and ezrin, and sensitizes target cells to interleukin-2-activated killing. These results reveal a new mechanism of target-cell recognition: cytotoxic cells recognize adhesion molecules that are already present on normal cells, but in diseased cells are concentrated into a biologically active cell-surface region by cytoskeletal reorganization. The results also highlight the importance of cytoskeletal interactions in the regulation of ICAM-2-mediated adhesive phenomena.
Helander
T S
TS
Department of Pathology, University of Helsinki, Finland.
Carpén
O
O
Turunen
O
O
Kovanen
P E
PE
Vaheri
A
A
Timonen
T
T
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D002896:Chromosomes, Human, Pair 6; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D006822:Hybrid Cells; D007376:Interleukin-2 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099149:Ezrin
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D007376:Interleukin-2; D010750:Phosphoproteins; D000099149:Ezrin; C065289:ICAM2 protein, human