HUMAN VASCULAR SMOOTH-MUSCLE CELL-MONOCYTE INTERACTIONS AND METALLOPROTEINASE SECRETION IN CULTURE
HUMAN VASCULAR SMOOTH-MUSCLE CELL-MONOCYTE INTERACTIONS AND METALLOPROTEINASE SECRETION IN CULTURE
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DOI：
10.1161/01.atv.15.12.2284
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发表时间：
1995-12-01
影响因子：
8.7
通讯作者：
LEE, RT
中科院分区：
文献类型：
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作者：
LEE, E;GRODZINSKY, AJ;LEE, RT
动脉粥样硬化斑块细胞外基质的降解会破坏病变的稳定性，使其更容易破裂。巨噬细胞和血管平滑肌细胞（SMCs）都是基质金属蛋白酶（MMPs）的潜在来源，MMPs是一种可以消化血管基质的分泌酶。我们探索了人血管SMCs和人单核细胞之间的相互作用，导致间质胶原酶（MMP-1）和基质溶解素（MMP-3）的分泌。单核细胞单独或用smc培养基处理的单核细胞不分泌这些金属蛋白酶，这是通过Western blot分析检测到的。SMCs与单核细胞共培养或用单核细胞条件培养基处理时，MMP-1和MMP-3的分泌量增加了20倍以上。在单核细胞和SMCs共培养中加入巨噬细胞集落刺激因子（小于或等于1000 U/mL）对金属蛋白酶分泌没有影响。重组白细胞介素(IL)-1受体拮抗剂可抑制SMC培养中MMP-1和MMP-3的诱导（分别减少94%和96%），而肿瘤坏死因子- α中和抗体对金属蛋白酶分泌无显著影响。与单核细胞条件培养基诱导SMCs分泌MMP-1和MMP-3相比，单核细胞条件培养基不增加72-kD明胶酶（MMP-2）的分泌。因此，单核细胞通过il -1依赖机制诱导血管SMCs分泌MMP-1和MMP-3。这种SMCs对特定巨噬细胞产物的反应可能有助于病变中单个核吞噬细胞破坏斑块的稳定。
Degradation of the atherosclerotic plaque extracellular matrix could destabilize the lesion, rendering it more prone to rupture. Both macrophages and vascular smooth muscle cells (SMCs) are potential sources of matrix metalloproteinases (MMPs), secreted enzymes that can digest vascular matrix. We explored interactions between human vascular SMCs and human monocytes that result in the secretion of interstitial collagenase (MMP-1) and stromelysin (MMP-3). Monocytes alone or those treated with SMC-conditioned media did not secrete these metalloproteinases as detectable by Western blot analysis. SMCs increased secretion of both MMP-1 and MMP-3 greater than 20-fold when cocultured with monocytes or when treated with monocyte-conditioned media. Addition of macrophage colony stimulating factor (less than or equal to 1000 U/mL) to cocultures of monocytes and SMCs did not affect metalloproteinase secretion. Recombinant interleukin (IL)-1 receptor antagonist inhibited MMP-1 and MMP-3 induction in SMC cultures treated with monocyte-conditioned media (94% and 96% reduction, respectively), while a neutralizing antibody to tumor necrosis factor-alpha had no significant effect on metalloproteinase secretion, In contrast to the induction by monocyte-conditioned media of MMP-1 and MMP-3 secretion by SMCs, monocyte-conditioned media did not increase secretion of 72-kD gelatinase (MMP-2). Thus, monocytes induce MMP-1 and MMP-3 secretion by vascular SMCs through an IL-1-dependent mechanism. This response of SMCs to a defined macrophage product may contribute to plaque destabilization by mononuclear phagocytes in the lesion.