Neutrophil emigration in the lungs, peritoneum, and skin does not require gelatinase B
Neutrophil emigration in the lungs, peritoneum, and skin does not require gelatinase B
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DOI：
10.1165/ajrcmb.20.6.3558
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发表时间：
1999-06-01
影响因子：
6.4
通讯作者：
Senior, RM
中科院分区：
文献类型：
--
作者：
Betsuyaku, T;Shipley, JM;Senior, RM
多形核白细胞（PMN）释放明胶酶B响应可变的刺激。明胶酶B在体外降解基底膜成分，并且抑制基质金属蛋白酶活性使PMN通过原型基底膜（Matrigel）和粘附性膜的迁移变钝。因此，已经推测明胶酶B对于PMN迁移是必需的。为了验证这一假设，我们在明胶酶B基因无效突变（明胶酶B-/-）和同窝对照（明胶酶B+/+）小鼠的肺、腹膜和皮肤中诱导急性炎症。在气管内滴注LPS后3、6、12和24 h，肺内PMN的移出（通过支气管肺泡灌洗液中的PMN测定）在明胶酶B-/-和明胶酶B+/+小鼠中相似。PMN的数量：在明胶酶B-/-和明胶酶B+/+小鼠中，巯基乙酸盐诱导的腹膜炎后4小时腹膜腔的变化也相当。皮内注射白细胞介素8后3 h，明胶酶B-/-和明胶酶B+/+小鼠真皮血管外均可见大量中性粒细胞，两种小鼠注射部位皮肤髓过氧化物酶活性无明显差异。来自明胶酶B-/-小鼠的PMN响应于具有thr的酵母聚糖活化血清而迁移通过Matrigel：与来自明胶酶B+/+小鼠的PMN具有相同的效率。在体外，明胶酶B-/- PMN与明胶酶B+/+小鼠的PMN一样有效地杀死金黄色葡萄球菌和肺炎克雷伯菌。这些结果表明，明胶酶B是不需要的中性粒细胞的迁移，并建议，尽管明胶酶B缺乏中性粒细胞的抗菌功能被保存。
Polymorphonuclear leukocytes (PMN) release gelatinase B in response to variable stimuli. Gelatinase B degrades basement membrane components in vitro, and inhibition of matrix metalloproteinase activity blunts PMN migration through a prototype basement membrane (Matrigel) and amnionic membranes, Accordingly, it has been speculated that gelatinase B is necessary for PMN emigration. To test this hypothesis we induced acute inflammation in the lungs, peritoneum, and skin in mice with a null mutation of the gelatinase B gene (gelatinase B-/-) and littermate controls (gelatinase B+/+). At 3, 6, 12, and 24 h after intratracheal instillation of LPS, the emigration of PMN in the lung, as determined by PMN in bronchoalveolar lavage fluid, was similar in gelatinase B-/- and gelatinase B+/+ mice. The number of PMN in the: peritoneal cavity 4 h after thioglycollate-induced peritonitis was also comparable in gelatinase B-/- and gelatinase B+/+ mice. At 3 h after an intradermal injection of interleukin-8, numerous PMN were present extravascularly in the dermis in both gelatinase B-/- and gelatinase B+/+ mice and the myeloperoxidase activities of the skin at the injection sites were indistinguishable between the two types of mice. PMN from gelatinase B-/- mice migrated through Matrigel in response to zymosan-activated serum with thr: same efficiency as did PMN from gelatinase B+/+ mice. In vitro, gelatinase B-/- PMN killed Staphylococcus aureus and Klebsiella pneumoniae as effectively as did PMN from gelatinase B+/+ mice. These findings indicate that gelatinase B is not required for PMN emigration, and suggest that the antibacterial function of PMN is preserved despite gelatinase B deficiency.