Matrix metalloprotease-9 release from monocytes increases as a function of differentiation: implications for neuroinflammation and neurodegeneration

• Published in: Journal of neuroimmunology Vol. 109; no. 2; pp. 221 - 227
• Main Authors: Vos, Catharina M.P., Gartner, Suzanne, Ransohoff, Richard M., McArthur, Justin C., Wahl, Larry, Sjulson, Lucas, Hunter, Edward, Conant, Katherine
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 22-09-2000
• Subjects: CCR-2; CCR2 protein; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cells, Cultured; Chemokine CCL2 - metabolism; Cytokines - pharmacology; Flow Cytometry; Humans; Matrix Metalloproteinase 9 - metabolism; MCP-1; MMP-9; monocyte chemoattractant protein 1; Monocytes; Monocytes - cytology; Monocytes - enzymology; Monocytes - immunology; Nerve Degeneration - enzymology; Nerve Degeneration - immunology; Neuritis - enzymology; Neuritis - immunology; Receptors, CCR2; Receptors, Chemokine - metabolism; CCR-2; MCP-1; Monocytes; MMP-9
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(00)00308-8

Naı̈ve monocytes extravasate in response to monocyte chemoattractant-1 (MCP-1) and subsequently, following differentiation within tissue, carry out effector functions. Consistent with this concept, expression of the MCP-1 receptor CCR2 decreases with monocyte differentiation, as production of cytokines increases (
Fantuzzi et al., 1999). Because matrix metalloproteases (MMPs) may also play an important role in the ability of monocytes to migrate into tissues and/or to promote pathogen clearance/tissue injury, we have examined production of matrix metalloprotease-9 as a function of both monocyte differentiation in vitro and expression of CCR2. Increased time in culture, which is linked to monocyte differentiation, resulted in enhanced production of MMP-9, assessed by gelatin substrate zymography. Further, CCR2-negative monocytes produced greater quantities of MMP-9 than did naı̈ve CCR2-positive cells. Our results indicate that MMP-9 release increases during monocyte differentiation, consistent with a prominent role in effector functions. Because extracellular matrix proteins are important to cell structure and survival (
Wee Yong et al., 1998), increased expression of MMP-9 could contribute to tissue damage following monocyte differentiation.