Matrix metalloprotease-9 release from monocytes as a function of differentiation

The expression of the monocyte chemoattractant-1 (MCP-1) receptor CCR-2 decreases with monocyte differentiation while the production of cytokines including MCP-1 increases. It has been hypothesized that monocytes must be able to migrate in response to MCP-1 when naive and then, following differentiation within tissue, to attract additional inflammatory cells. Because matrix metalloproteases (MMPs) may also be involved in the ability of monocytes to migrate into tissues, and because studies have shown increased production of select proteases by MCP-1 responsive versus non-responsive monocytes, we examined MMP-9 production as a function of both monocyte differentiation and expression of CCR-2. Interestingly, culture of either adherence purified or elutriated monocytes for 5 days was associated with increased production of MMP-9 as assessed by gelatin substrate zymography. In addition, CCR-2 negative monocytes produced greater quantities of MMP-9 than did CCR-2 positive. Relatively lower expression of MMP-9 may not improve the ability of naive/relatively undifferentiated monocytes to migrate into select tissues. Nonetheless, relatively increased expression of MMP-9 could contribute to tissue damage following monocyte differentiation.