The integral membrane, Kunitz-type serine protease inhibitors HAI-1 and HAI-2, can suppress the proteolytic activity of the type 2 transmembrane serine protease matriptase with high specificity and potency. High levels of extracellular matriptase proteolytic activity have, however, been observed in some neoplastic B-cells with high levels of endogenous HAI-2, indicating that HAI-2 may be an ineffective matriptase inhibitor at the cellular level. The different effectiveness of the HAIs in the control of extracellular matriptase proteolytic activity is examined here. Upon inducing matriptase zymogen activation in the HAI Teton Daudi Burkitt lymphoma cells, which naturally express matriptase with very low levels of HAI-2 and no HAI-1, nascent active matriptase was rapidly inhibited or shed as an enzymatically active enzyme. With increasing HAI-1 expression, cellular matriptase-HAI-1 complex increased, and extracellular active matriptase decreased proportionally. Increasing HAI-2 expression, however, resulted in cellular matriptase-HAI-2 complex levels reaching a plateau, while extracellular active matriptase remained high. In contrast to this differential effect, both HAI-1 and HAI-2, even at very low levels, were shown to promote the expression and cell-surface translocation of endogenous matriptase. The difference in the suppression of extracellular active matriptase by the two closely related serine protease inhibitors could result from the primarily cell surface expression of HAI-1 compared to the mainly intracellular localization of HAI-2. The HAIs, therefore, resemble one another with respect to promoting matriptase expression and surface translocation but differ in their effectiveness in the control of extracellular matriptase enzymatic activity.

完整的膜，Kunitz 型丝氨酸蛋白酶抑制剂 HAI-1 和 HAI-2，可以抑制 2 型跨膜丝氨酸蛋白酶基质蛋白酶的蛋白水解活性，具有高特异性和效力。然而，在一些具有高水平内源性 HAI-2 的肿瘤 B 细胞中观察到高水平的细胞外基质蛋白酶蛋白水解活性，表明 HAI-2 在细胞水平上可能是无效的基质蛋白酶抑制剂。此处检查了 HAI 在控制细胞外基质酶蛋白水解活性方面的不同有效性。在 HAI Teton Daudi Burkitt 淋巴瘤细胞中诱导 matriptase 酶原活化后，该细胞天然表达具有非常低水平的 HAI-2 且没有 HAI-1 的 matriptase，新生的活性 matriptase 被迅速抑制或作为酶活性酶脱落。随着HAI-1表达的增加，细胞matriptase-HAI-1复合物增加，细胞外活性matriptase按比例减少。然而，增加 HAI-2 表达导致细胞基质蛋白酶-HAI-2 复合物水平达到一个平台期，而细胞外活性基质蛋白酶仍然很高。与这种差异效应相反，HAI-1 和 HAI-2，即使在非常低的水平，也显示出促进内源性基质酶的表达和细胞表面易位。两种密切相关的丝氨酸蛋白酶抑制剂对细胞外活性基质蛋白酶抑制的差异可能是由于 HAI-1 的主要细胞表面表达与 HAI-2 的主要细胞内定位相比。因此，HAI