Interleukin-12 is chemotactic for natural killer cells and stimulates their interaction with vascular endothelium.
We investigated the chemotactic activity of interleukin (IL)-12 on human natural killer (NK) cells and other leukocyte subsets. It was found that IL-12 induced directional migration of highly enriched preparations of NK cells (> 80% CD16+ and CD56+) and CD3-activated T cells (both of CD4 and CD8 subset), but not resting T cells and monocytes. On the contrary, purified polymorphonuclear cells (PMN) showed significant and reproducible chemotactic response to IL-12. The effects of IL-12 on leukocyte migration were observed in a narrow concentration range with a peak at approximately 7.5 ng/mL, and were abrogated by monoclonal antibody (MoAb) anti-IL-12 or after cytokine boiling. We also investigated the interaction of NK cells with vascular endothelium in vitro. Overnight treatment of NK cells with IL-12 augmented their binding to cultured endothelial cells (EC) obtained from umbilical veins. IL-12-increased binding was better observed when resting rather than IL-1-activated EC were used as substratum of adhesion. IL-12-augmented binding of NK cells to resting or IL-1-activated EC involved the LFA-1/ICAM-1 and VLA-4/VCAM-1 pathways. Thus, by inducing migration and interaction with EC, IL-12 regulates crucial determinants of NK-cell recruitment in tissues.
Allavena
P
P
Department of Immunology, Mario Negri Institute, Milano, Italy.
Paganin
C
C
Zhou
D
D
Bianchi
G
G
Sozzani
S
S
Mantovani
A
A
D017252:CD3 Complex / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D009504:Neutrophils / Q000502:physiology
D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018664:Interleukin-12