Abstract
BackgroundDuring infection and inflammation, circulating blood monocytes migrate from the intravascular compartments to the extravascular compartments, where they mature into tissue macrophages. The maturation process prepares the cells to actively participate in the inflammatory and immune responses, and many factors have been reported to be involved in the process. We found in our study that CD147 played a very important role in this process.ResultsBy using PMA-differentiated human monocyte cells line THP-1, we found that CD147 mediated matrix metalloproteinases (MMPs) expression of the leukemic THP-1 cells and thus enhanced the invasiveness of THP-1 cells. After 24 hours of PMA-induced monocyte differentiation, the mean fluorescence intensity of CD147 in differentiated THP-1 cells (289.61 ± 31.63) was higher than that of the undifferentiated THP-1 cells (205.1 ± 19.25). There was a significant increase of the levels of proMMP-2, proMMP-9 and their activated forms in the differentiated THP-1 cells. Invasion assays using reconstituted basement membrane showed a good correlation between the invasiveness of THP-1 cells and the production of MMP-2 and MMP-9. The difference in the MMPs expression and the invasive ability was significantly blocked by HAb18G/CD147 antagonistic peptide AP-9. The inhibitory rate of the secretion of proMMP-9 in the undifferentiated THP-1 cells was 45.07%. The inhibitory rate of the secretion of proMMP-9, the activated MMP-9 and proMMP-2 in the differentiated THP-1 cells was 52.90%, 53.79% and 47.80%, respectively. The inhibitory rate of invasive potential in the undifferentiated cells and the differentiated THP-1 cells was 41.82 % and 25.15%, respectively.ConclusionThe results suggest that the expression of CD147 is upregulated during the differentiation of monocyte THP-1 cells to macrophage cells, and CD147 induces the secretion and activation of MMP-2 and MMP-9 and enhances the invasive ability of THP-1 cells. The matured monocytes / macrophages, via their high expression of CD147, may play an important role in promoting the tissue repair or tissue damage during their inflammatory response.
Highlights
During infection and inflammation, circulating blood monocytes migrate from the intravascular compartments to the extravascular compartments, where they mature into tissue macrophages
In this study we demonstrate that the overexpression of CD147 enhances the release and the activation of matrix metalloproteinases (MMPs) (MMP-2 and MMP-9) and the invasive potential during the differentiation of monocyte THP-1 cells to macrophage cells
In view of the fact that CD147 may be required for the expression of gelatinases MMP-2 and MMP-9 and that the gelatinases MMP-2 and MMP-9 are expressed in leukemic cells [19,20,26], our study focused on the potential interaction between CD147 and MMPs, MMP-2 and MMP-9, in the differentiation process of monocytes into macrophages and in the invasion of monocytes/macrophages
Summary
During infection and inflammation, circulating blood monocytes migrate from the intravascular compartments to the extravascular compartments, where they mature into tissue macrophages. The maturation process prepares the cells to actively participate in the inflammatory and immune responses, and many factors have been reported to be involved in the process. We found in our study that CD147 played a very important role in this process. Activated macrophages are known to play an important role in the degradation process of normal and abnormal matrix. The response of macrophages to pathogens is markedly enhanced, allowing them to participate in the inflammatory and immune responses [1]. The activated inflammatory macrophage plays a crucial role in matrix destruction by producing matrix metalloproteinases (MMPs) both directly and indirectly [3,4,5]. In the studies of kidney disease, inflammatory macrophages of the glomeruli are found to have induced myofibroblast mesangial cells to produce stromelysin (MMP-3) [9]
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