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

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.