M. tuberculosis induction of matrix metalloproteinase-9: the role of mannose and receptor-mediated mechanisms.

Authors

• Carlos A Rivera-Marrero
• William Schuyler
• Susanne Roser
• Jeffrey D Ritzenthaler
• Sarah A Newburn
• Jesse Roman

Publication/Presentation Date

3-1-2002

Abstract

Mycobacterium tuberculosis (Mtb) infection induces the expression of matrix metalloproteinase-9 (MMP-9) in mouse lungs. In cultured human monocytic cells, Mtb bacilli and the cell wall glycolipid lipoarabinomannan (LAM) stimulate high levels of MMP-9 activity. Here, we explore the cellular mechanisms involved in the induction of MMP-9 by Mtb. We show that infection of THP-1 cells with Mtb caused a fivefold increase in MMP-9 mRNA that was associated with increased MMP-9 activity. MMP-9 induction was dependent on microtubule polymerization and protein kinase activation and was associated with increased DNA binding by the transcription factor activator protein-1 (AP-1), which appeared to be important for MMP-9 expression. We then explored the surface molecules potentially involved in Mtb induction of MMP-9, focusing on ligands of the mannose and beta-glucan receptors. MMP-9 activity was induced by the mannose receptor ligands mannan, zymosan, and LAM, whereas the beta-glucan receptor ligand laminarin was not effective. The most active inducers of MMP-9 activity were the particulate ligand zymosan and LAM. Pretreatment of cells with an anti-mannose receptor monoclonal antibody, but not anti-complement receptor 3, decreased the induction of MMP-9 activity by Mtb bacilli. Together, these results suggest that MMP-9 induction by Mtb occurs by receptor-mediated signaling mechanisms involving the binding of mannosylated ligands to mannose receptors, the modulation by cytoskeletal elements such as microtubules, the activation of protein kinases, and transcriptional activation by AP-1.

Volume

282

Issue

3

First Page

546

Last Page

555

ISSN

1040-0605

Published In/Presented At

Rivera-Marrero, C. A., Schuyler, W., Roser, S., Ritzenthaler, J. D., Newburn, S. A., & Roman, J. (2002). M. tuberculosis induction of matrix metalloproteinase-9: the role of mannose and receptor-mediated mechanisms. American journal of physiology. Lung cellular and molecular physiology, 282(3), L546–L555. https://doi.org/10.1152/ajplung.00175.2001

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

11839551

Department(s)

Administration and Leadership

Document Type

Article