MAST-CELL PROTEINASES ACTIVATE PRECURSOR FORMS OF COLLAGENASE AND STROMELYSIN, BUT NOT OF GELATINASE-A AND GELATINASE-B
MAST-CELL PROTEINASES ACTIVATE PRECURSOR FORMS OF COLLAGENASE AND STROMELYSIN, BUT NOT OF GELATINASE-A AND GELATINASE-B
复制标题
DOI：
10.1111/j.1432-1033.1994.tb18980.x
复制
发表时间：
1994-07-01
期刊：
影响因子：
--
通讯作者：
WOOLLEY, DE
中科院分区：
文献类型：
--
作者：
LEES, M;TAYLOR, DJ;WOOLLEY, DE
体内肥大细胞的激活通常与水肿区和结缔组织降解有关。类胰蛋白酶和糜酶是肥大细胞释放的主要丝氨酸蛋白酶，但它们对细胞外基质的大部分成分几乎没有活性。基质金属蛋白酶(MMPs)被认为能降解几乎所有的结缔组织成分，由细胞以非活性前体的形式分泌。由于体内对基质金属蛋白酶的激活机制知之甚少，我们研究了肥大细胞蛋白酶激活人胶原酶(MMP1)、基质分解酶(MMP3)、明胶酶A(MMP2)和明胶酶B(MMP9)前体形式的可能性。从纯化的狗肥大细胞瘤细胞中制备的肥大细胞蛋白酶可以处理和激活纯化的MMP1和MMP3前体形式。分别用类胰蛋白酶和糜乳酶的抑制剂止痛和乳糜抑素，证明PMMP-1和PMMP-3都能被糜酶组分有效地处理和激活。相比之下，类胰蛋白酶仅激活PMMP-3。肥大细胞蛋白酶不能处理或激活纯化的基质金属蛋白酶-2和基质金属蛋白酶-9的前体形式。然而，先前被肥大细胞蛋白水解酶激活的基质金属蛋白酶-3被证明可以激活PMMP-9，但不能激活PMMP-2。由于我们没有证据表明肥大细胞表达这四种金属酶，肥大细胞激活/脱颗粒后释放的丝氨酸蛋白酶可能有助于局部金属蛋白酶的激活和随后的基质降解。
Mast cell activation in vivo is often associated with areas of oedema and connective-tissue degradation. Tryptase and chymase are the major serine proteinases released by mast cells, but they appear to have little activity on most components of the extracellular matrix. The matrix metalloproteinases (MMP) are purported to degrade almost all connective tissue elements and are secreted by cells in the form of inactive precursors. Since the mechanisms of MMP activation in vivo are poorly understood we have examined the potential of mast cell proteinases to activate the precursor forms of human collagenase (MMP-1), stromelysin (MMP-3), gelatinase A (MMP-2) and gelatinase B (MMP-9).Mast cell proteinases prepared from purified dog mastocytoma cells were shown to process and activate purified precursor forms of both MMP-1 and MMP-3. Using antipain and chymostatin, inhibitors for tryptase and chymase, respectively, it was demonstrated that both pMMP-1 and pMMP-3 were effectively processed and activated by the chymase component. By contrast, tryptase activated only pMMP-3. The mast cell proteinases were unable to process or activate purified precursor forms of MMP-2 and MMP-9. However, MMP-3 previously activated by mast cell proteinases was shown to activate pMMP-9, but not pMMP-2. Since we have no evidence that mast cells express these four metalloenzymes, the release of mast cell serine proteinases following activation/degranulation could contribute to local metalloproteinase activation and subsequent matrix degradation.