Neutral metalloproteinases produced by human mononuclear phagocytes. Enzyme profile, regulation, and expression during cellular development.
Neutral metalloproteinases produced by human mononuclear phagocytes. Enzyme profile, regulation, and expression during cellular development.
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DOI：
10.1172/jci114867
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发表时间：
1990-11
期刊：
影响因子：
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通讯作者：
H. Welgus;E. J. Campbell;J D Cury;A. Z. Eisen;R. M. Senior;S. Wilhelm;G. I. Goldberg
中科院分区：
文献类型：
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作者：
H. Welgus;E. J. Campbell;J D Cury;A. Z. Eisen;R. M. Senior;S. Wilhelm;G. I. Goldberg
单核吞噬细胞是发育和功能复杂的细胞，在细胞外基质重塑中发挥关键作用。我们假设以肺泡巨噬细胞为代表的分化单核吞噬细胞使用一系列金属蛋白酶来降解各种基质大分子。为了检验这一假设，我们评估了人单核吞噬细胞对四种金属蛋白酶（间质胶原酶、溶基质素、72-kD IV 型胶原酶和 92-kD IV 型胶原酶）的合成和分泌，涉及（a）细胞分化的影响，（b）分泌调节，以及（c）与原型金属蛋白酶分泌细胞（人成纤维细胞）的比较/对比。我们发现，更大数量和更广谱的金属酶的调节分泌与更加分化的细胞表型相关。作为极端的例子，92-kD IV 型胶原酶由外周血单核细胞和未诱导的 U937 单核细胞样细胞释放，而溶基质素仅由脂多糖刺激的肺泡巨噬细胞分泌。巨噬细胞产生的间质胶原酶、溶基质素和 72-kD IV 型胶原酶分别约为同等数量成纤维细胞的 20%、10% 和 1-2%；成纤维细胞不共享 92-kD IV 型胶原酶的分泌。这项工作证实了巨噬细胞通过分泌的金属蛋白酶直接降解细胞外基质的潜力，其方式在质量和数量上都不同于成纤维细胞。此外，可以在该模型系统中在分子水平上研究金属酶合成的不同调节（通过分化过程中基础分泌和刺激分泌的不同模式来证明）。
Mononuclear phagocytes are developmentally and functionally complex cells that play critical roles in extracellular matrix remodeling. We hypothesized that differentiated mononuclear phagocytes, typified by alveolar macrophages, use a spectrum of metalloproteinases to degrade various matrix macromolecules. To test this hypothesis, we have evaluated synthesis and secretion of four metalloproteinases (interstitial collagenase, stromelysin, 72-kD type IV collagenase, and 92-kD type IV collagenase) by human mononuclear phagocytes with regard to (a) the effect of cellular differentiation, (b) regulation of secretion, and (c) comparisons/contrasts with a prototype metalloproteinase-secretory cell, the human fibroblast. We found that regulated secretion of greater quantities and a wider spectrum of metalloenzymes correlated with a more differentiated cellular phenotype. As extreme examples, the 92-kD type IV collagenase was released by peripheral blood monocytes and uninduced U937 monocyte-like cells, whereas stromelysin was secreted only by lipopolysaccharide-stimulated alveolar macrophages. Macrophage production of interstitial collagenase, stromelysin, and 72-kD type IV collagenase was approximately 20%, 10%, and 1-2%, respectively, of that from equal numbers of fibroblasts; secretion of the 92-kD type IV collagenase was not shared by fibroblasts. This work confirms the potential of macrophages to directly degrade extracellular matrix via secreted metalloproteinases in a manner that differs both qualitatively and quantitatively from that of fibroblasts. Moreover, varying regulation of metalloenzyme synthesis, evidenced by distinct patterns of basal and stimulated secretion during differentiation, can be studied at a molecular level in this model system.