Function of lymphocyte homing-associated adhesion molecules on human natural killer and lymphokine-activated killer cells.
We have analyzed the ability of fresh and rIL-2-activated human NK cells to interact with high endothelial venules (HEV) that are known to support physiologic lymphocyte extravasation, and examined the role of different adhesion molecules in this process. In in vitro HEV-binding assays, NK cells bound to both peripheral lymph node (pLN) and mucosal HEV. Activation by rIL-2 slightly decreased adherence to pLN HEV, but increased adherence to mucosal high endothelium. Markedly fewer NK cells than PBL expressed L-selectin, and the expression was diminished further upon treatment with rIL-2. Inhibition studies showed, however, that L-selectin was the most important single molecule to mediate adhesion to pLN HEV. Binding to mucosal HEV was mediated mainly by CD44 and alpha 4 integrin, and the expression level of these molecules was increased by rIL-2, paralleling the results in HEV-binding assays. Higher m.w. forms of CD44, representing differentially glycosylated/variant forms of CD44, were more abundant on large granular lymphocytes than on unseparated PBL. We conclude that, despite weak recirculatory capacity, NK cells or a subpopulation of NK cells with the correct adhesion molecules can interact with and bind to high endothelial cells. Lymphokines can modulate the expression of adhesion molecules that NK cells utilize for HEV binding. Our results suggest that activation of NK cells with IL-2 may facilitate the extravasation of lymphokine-activated killer cells, especially to mucosal sites, whereas homing to peripheral lymphoid tissues may be diminished. This should be taken into consideration when procedures for lymphokine-activated killer cell immunotherapy are planned.
Uksila
J
J
Department of Medical Microbiology, Turku University, Finland.
Salmi
M
M
Butcher
E C
EC
Tarkkanen
J
J
Jalkanen
S
S
D004729:Endothelium, Lymphatic / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry; D007399:Interphase / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D008213:Lymphocyte Activation; D017452:Receptors, IgG / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis / Q000502:physiology*
D018960:Hyaluronan Receptors; D017452:Receptors, IgG; D016201:Receptors, Lymphocyte Homing