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Interleukin-12 is chemotactic for natural killer cells and stimulates their
interaction with vascular endothelium
P Allavena, C Paganin, D Zhou, G Bianchi, S Sozzani and A Mantovani
Department of Immunology, Mario Negri Institute, Milano, Italy.
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.
Volume 84,
Issue 7,
pp. 2261-2268,
10/01/1994
Copyright © 1994 by The American Society of Hematology
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