Buckmaster M J, Curci J A, Murray P R, Liao S, Allen B T, Sicard G A, Thompson R W
Department of Surgery, Washington University School of Medicine, St Louis, MI 63110, USA.
Cardiovasc Surg. 1999 Jan;7(1):16-26. doi: 10.1016/s0967-2109(98)00099-4.
Elastolytic matrix metalloproteinases play a central role in the development of chronic atherosclerotic aortic aneurysms, but mycotic aortic aneurysms are a distinct and unusual form of aneurysm disease caused by bacterial infection. Mycotic aortic aneurysms follow a more rapid and unpredictable course than chronic aneurysm disease and they exhibit a predilection for the suprarenal aorta, further implying unique pathophysiologic mechanisms. The purpose of this study was to examine the nature and source of elastin-degrading enzymes in mycotic aortic aneurysm. Bacterial isolates and aortic tissues were obtained from four consecutive patients undergoing surgical repair of suprarenal mycotic aortic aneurysm. Using an in vitro 3H-labeled elastin degradation assay, elastin-degrading enzyme activity was only observed in the bacteria-conditioned medium from an isolate of Pseudomonas aeruginosa. Elastin-degrading enzyme activity in the aortic tissue homogenate of this patient was abolished by the serine protease inhibitor, phenylmethylsulfonyl fluoride, but it was not suppressed by the metalloproteinase inhibitor, ethylenediamine tetraacetic acid (EDTA). In contrast, elastin-degrading enzyme activity in the bacterial-conditioned medium was decreased by about half by both phenylmethylsulfonyl fluoride and EDTA. Elastin substrate zymography revealed two phenylmethylsulfonyl fluoride-inhibitable elastin-degrading enzyme activities in the aortic tissue homogenate that corresponded to human neutrophil elastase (approximately 30 kDa) and its stable complex with alpha 1-proteinase inhibitor (approximately 80 kDa), but no activity attributable to Pseudomonas elastase, a 33-kDa metal-dependent enzyme. Human neutrophil elastase was readily detected throughout mycotic aortic aneurysm tissues by immunohistochemistry, but elastolytic metalloproteinases were only occasionally observed. The results of this study suggest that the elastin-degrading enzyme produced in mycotic aortic aneurysm are largely serine proteases of host neutrophil origin, rather than elastases produced by the infecting microorganisms or the macrophage-derived metalloproteinases typically observed in atherosclerotic aneurysm disease. Further studies will be needed to extend these findings to a larger number of patients with mycotic aortic aneurysm and those caused by additional microorganisms.
弹性蛋白酶解基质金属蛋白酶在慢性动脉粥样硬化性主动脉瘤的发展中起核心作用，但霉菌性主动脉瘤是由细菌感染引起的一种独特且不常见的动脉瘤疾病形式。霉菌性主动脉瘤比慢性动脉瘤疾病发展得更快且更不可预测，并且它们更倾向于累及肾上腺上方的主动脉，这进一步暗示了其独特的病理生理机制。本研究的目的是检查霉菌性主动脉瘤中弹性蛋白降解酶的性质和来源。从连续4例接受肾上腺上方霉菌性主动脉瘤手术修复的患者中获取细菌分离株和主动脉组织。使用体外3H标记的弹性蛋白降解试验，仅在铜绿假单胞菌分离株的细菌条件培养基中观察到弹性蛋白降解酶活性。该患者主动脉组织匀浆中的弹性蛋白降解酶活性被丝氨酸蛋白酶抑制剂苯甲基磺酰氟消除，但未被金属蛋白酶抑制剂乙二胺四乙酸（EDTA）抑制。相比之下，苯甲基磺酰氟和EDTA均可使细菌条件培养基中的弹性蛋白降解酶活性降低约一半。弹性蛋白底物酶谱分析显示，主动脉组织匀浆中有两种可被苯甲基磺酰氟抑制的弹性蛋白降解酶活性，分别对应于人中性粒细胞弹性蛋白酶（约30 kDa）及其与α1-蛋白酶抑制剂的稳定复合物（约80 kDa），但未检测到与假单胞菌弹性蛋白酶（一种33 kDa的金属依赖性酶）相关的活性。通过免疫组织化学在整个霉菌性主动脉瘤组织中很容易检测到人中性粒细胞弹性蛋白酶，但仅偶尔观察到弹性蛋白酶解基质金属蛋白酶。本研究结果表明，霉菌性主动脉瘤中产生的弹性蛋白降解酶主要是宿主中性粒细胞来源的丝氨酸蛋白酶，而非感染微生物产生的弹性蛋白酶或动脉粥样硬化性动脉瘤疾病中常见的巨噬细胞衍生的金属蛋白酶。需要进一步研究将这些发现扩展到更多患有霉菌性主动脉瘤的患者以及由其他微生物引起的患者。
