This Article Full Text Free Full Text (PDF) Free Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vaday, G. G. Articles by Lider, O. Search for Related Content PubMed PubMed Citation Articles by Vaday, G. G. Articles by Lider, O.

(Journal of Leukocyte Biology. 2000;68:737-747.)
© 2000 by Society for Leukocyte Biology

Fibronectin-bound TNF- stimulates monocyte matrix metalloproteinase-9 expression and regulates chemotaxis

Gayle G. Vaday^*, Rami Hershkoviz, Michal A. Rahat, Nitza Lahat, Liora Cahalon^* and Ofer Lider^*

^* Department of Immunology, The Weizmann Institute of Science, Rehovot;
Department of Internal Medicine, Meir Hospital, Kfar Saba; and
Immunology Research Unit, Lady Davis Carmel Medical Center, Haifa, Israel

Correspondence: Ofer Lider, Ph.D., Dept. of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel. E-mail: ofer.lider{at}weizmann.ac.il

Tumor necrosis factor (TNF-) is a proinflammatory cytokine implicated in the stimulation of matrix metalloproteinase (MMP) production by several cell types. Our previous studies demonstrated that TNF- avidly binds fibronectin (FN) and laminin, major adhesive glycoproteins of extracellular matrix (ECM) and basement membranes. These findings suggested that TNF- complexing to insoluble ECM components may serve to concentrate its activities to distinct inflamed sites. Herein, we explored the bioactivity and possible function of ECM-bound TNF- by examining its effects on MMP-9 secretion by monocytes. Immunofluorescent staining indicated that LPS-activated monocytes deposited newly synthesized TNF- into ECM-FN. FN-bound TNF- (FN/TNF-) significantly up-regulated MMP-9 expression and secretion by the human monocytic cell line MonoMac-6 and peripheral blood monocytes. Such secretion could be inhibited by antibodies that block TNF- activity and binding to its receptors TNF RI (p55) and TNF RII (p75). Chemotaxis through ECM gels in the presence of soluble or bound TNF- was inhibited by a hydroxamic acid inhibitor of MMPs (GM6001). It is interesting that, although the adhesion of MonoMac-6 cells to FN/TNF- required functional activated ß₁ integrins, FN/TNF--induced MMP-9 secretion was independent of binding to ß₁ integrins, since MMP-9 secretion was unaffected by: (1) neutralizing mAb to 4, 5, and ß1 subunits, which blocked cell adhesion; (2) a mAb that stimulated ß₁ integrin-mediated adhesion; and (3) binding TNF- to the 30-kDa amino-terminal fragment of FN, which lacks the major cell adhesive binding sites. Thus, in addition to their cell-adhesive roles, ECM glycoproteins, such as FN, may play a pivotal role in presenting proinflammatory cytokines to leukocytes within the actual inflamed tissue, thereby affecting their capacities to secrete ECM-degrading enzymes. These TNF--ECM interactions may serve to limit the cytokine’s availability and bioactivity to target areas of inflammation.

Key Words: inflammation • gelatinase • extracellular matrix

This article has been cited by other articles:

				T. Baranek, R. Debret, F. Antonicelli, B. Lamkhioued, A. Belaaouaj, W. Hornebeck, P. Bernard, M. Guenounou, and R. Le Naour Elastin Receptor (Spliced Galactosidase) Occupancy by Elastin Peptides Counteracts Proinflammatory Cytokine Expression in Lipopolysaccharide-Stimulated Human Monocytes through NF-{kappa}B Down-Regulation J. Immunol., November 1, 2007; 179(9): 6184 - 6192. [Abstract] [Full Text] [PDF]

				A-H. Kwon, Z. Qiu, K. Tsuji, T. Miyaso, and T. Okumura Fibronectin Prevents Endotoxin Shock After Partial Hepatectomy in Rats via Inhibition of Nuclear Factor-{kappa}B and Apoptosis Exp Biol Med, July 1, 2007; 232(7): 895 - 903. [Abstract] [Full Text] [PDF]

				B. Marom, M. A. Rahat, N. Lahat, L. Weiss-Cerem, A. Kinarty, and H. Bitterman Native and fragmented fibronectin oppositely modulate monocyte secretion of MMP-9 J. Leukoc. Biol., June 1, 2007; 81(6): 1466 - 1476. [Abstract] [Full Text] [PDF]

				M. T. Imtiaz, J. H. Schripsema, I. M. Sigar, J. N. Kasimos, and K. H. Ramsey Inhibition of Matrix Metalloproteinases Protects Mice from Ascending Infection and Chronic Disease Manifestations Resulting from Urogenital Chlamydia muridarum Infection Infect. Immun., October 1, 2006; 74(10): 5513 - 5521. [Abstract] [Full Text] [PDF]

				K. B. Holven, B. Halvorsen, V. Bjerkeli, J. K. Damas, K. Retterstol, L. Morkrid, L. Ose, P. Aukrust, and M. S. Nenseter Impaired Inhibitory Effect of Interleukin-10 on the Balance Between Matrix Metalloproteinase-9 and Its Inhibitor in Mononuclear Cells From Hyperhomocysteinemic Subjects Stroke, July 1, 2006; 37(7): 1731 - 1736. [Abstract] [Full Text] [PDF]

				S. Blazquez, C. Zimmer, G. Guigon, J.-C. Olivo-Marin, N. Guillen, and E. Labruyere Human Tumor Necrosis Factor is a Chemoattractant for the Parasite Entamoeba histolytica Infect. Immun., February 1, 2006; 74(2): 1407 - 1411. [Abstract] [Full Text] [PDF]

				A. Kipar, H. May, S. Menger, M. Weber, W. Leukert, and M. Reinacher Morphologic Features and Development of Granulomatous Vasculitis in Feline Infectious Peritonitis Veterinary Pathology, May 1, 2005; 42(3): 321 - 330. [Abstract] [Full Text] [PDF]

				A. L. Chancey, G. L. Brower, and J. S. Janicki Cardiac mast cell-mediated activation of gelatinase and alteration of ventricular diastolic function Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2152 - H2158. [Abstract] [Full Text] [PDF]

				G. A. Limb, J. T. Daniels, R. Pleass, D. G. Charteris, P. J. Luthert, and P. T. Khaw Differential Expression of Matrix Metalloproteinases 2 and 9 by Glial Muller Cells : Response to Soluble and Extracellular Matrix-Bound Tumor Necrosis Factor-{alpha} Am. J. Pathol., May 1, 2002; 160(5): 1847 - 1855. [Abstract] [Full Text] [PDF]

				G. G. Vaday, S. Franitza, H. Schor, I. Hecht, A. Brill, L. Cahalon, R. Hershkoviz, and O. Lider Combinatorial signals by inflammatory cytokines and chemokines mediate leukocyte interactions with extracellular matrix J. Leukoc. Biol., June 1, 2001; 69(6): 885 - 892. [Abstract] [Full Text] [PDF]

				G. G. Vaday, H. Schor, M. A. Rahat, N. Lahat, and O. Lider Transforming growth factor-{beta} suppresses tumor necrosis factor {alpha}-induced matrix metalloproteinase-9 expression in monocytes J. Leukoc. Biol., April 1, 2001; 69(4): 613 - 621. [Abstract] [Full Text]

				A. L. Chancey, G. L. Brower, and J. S. Janicki Cardiac mast cell-mediated activation of gelatinase and alteration of ventricular diastolic function Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2152 - H2158. [Abstract] [Full Text] [PDF]