IL-12 inhibition of endothelial cell functions and angiogenesis depends on lymphocyte-endothelial cell cross-talk

M. Strasly, F. Cavallo, M. Geuna, S. Mitola, M. P. Colombo, G. Forni, F. Bussolino

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

In vivo IL-12-dependent tumor inhibition rests on the ability of IL-12 to activate a CD8-mediated cytotoxicity, inhibit angiogenesis, and cause vascular injury. Although in vivo studies have shown that such inhibition stems from complex interactions of immune cells and the production of IFN-γ and other downstream angiostatic chemokines, the mechanisms involved are still poorly defined. Here we show that IL-12 activates an anti-angiogenic program in Con A-activated mouse spleen cells (activated spc) or human PBMC (activated PBMC). The soluble factors they release in its presence arrest the cycle of endothelial cells (EC), inhibit in vitro angiogenesis, negatively modulate the production of matrix metalloproteinase-9, and the ability of EC to adhere to vitronectin and up-regulate ICAM-1 and VCAM-1 expression. These effects do not require direct cell-cell contact, yet result from continuous interaction between activated lymphoid cells and EC. We used neutralizing Abs to show that the IFN-inducible protein-10 and monokine-induced by IFN-γ chemokines are pivotal in inducing these effects. Experiments with nu/nu mice, nonobese diabetic-SCID mice, or activated spc enriched in specific cell subpopulations demonstrated that CD4+, CD8+, and NK cells are all needed to mediate the full anti-angiogenetic effect of IL-12.

Original languageEnglish
Pages (from-to)3890-3899
Number of pages10
JournalJournal of Immunology
Volume166
Issue number6
Publication statusPublished - Mar 15 2001

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Interleukin-12
Endothelial Cells
Lymphocytes
Chemokines
Spleen
Monokines
Vitronectin
Inbred NOD Mouse
SCID Mice
Vascular Cell Adhesion Molecule-1
Vascular System Injuries
Matrix Metalloproteinase 9
Intercellular Adhesion Molecule-1
Antigen-Antibody Complex
Cell Communication
Natural Killer Cells
Up-Regulation
Neoplasms
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

IL-12 inhibition of endothelial cell functions and angiogenesis depends on lymphocyte-endothelial cell cross-talk. / Strasly, M.; Cavallo, F.; Geuna, M.; Mitola, S.; Colombo, M. P.; Forni, G.; Bussolino, F.

In: Journal of Immunology, Vol. 166, No. 6, 15.03.2001, p. 3890-3899.

Research output: Contribution to journalArticle

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AU - Forni, G.

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