Temporal expression of different pathways of 1-arginine metabolism in healing wounds.
Temporal expression of different pathways of 1-arginine metabolism in healing wounds.
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DOI：
10.4049/jimmunol.144.10.3877
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发表时间：
1990-05
影响因子：
4.4
通讯作者：
J. Albina;C. Mills;W. Henry;M. Caldwell
中科院分区：
文献类型：
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作者：
J. Albina;C. Mills;W. Henry;M. Caldwell
精氨酸可以通过至少两种途径被炎性细胞代谢。一种是氧化性L-精氨酸脱亚胺酶（OAD），可导致瓜氨酸和活性氮中间体的形成。另一种是鸟氨酸酶，它决定了鸟氨酸和尿素的产生。这些途径在实验伤口模型（s.c.通过检查植入后6小时至15天从海绵获得的流体中氨基酸和亚硝酸盐的浓度来研究大鼠中植入的聚乙烯醇海绵）。这些分析揭示了两个不同的时期，在此期间，液体中的精氨酸浓度明显低于血浆水平。在早期（海绵植入后不到3天），伤口液中瓜氨酸和亚硝酸盐含量高于其他任何时间，表明OAD活性。相比之下，在精氨酸浓度的晚期降低期间（延长超过第3天），鸟氨酸在液体中积累，在此期间，伤口液体也含有高精氨酸酶活性。在含有[guanido-14 C]-l-精氨酸的海绵培养物中证实了伤口中精氨酸代谢的不同途径的这种时间依赖性表达。植入后不到48小时收获的海绵中所含的细胞主要将标记精氨酸代谢为标记瓜氨酸，而在此时间后收获的海绵培养过程中产生标记尿素。伤口液的低精氨酸含量似乎并不限制晚期海绵中OAD表达的速率，因为当向培养物中加入4 mM精氨酸时，没有证明OAD活性。这些结果表明，在该模型中，OAD途径主要在修复的早期、多形核白细胞为主的阶段表达。此时，精氨酸代谢产生的活性氮中间体可能介导一些早期炎症特征性事件，包括微生物抑制、血管舒张和血小板聚集的抑制/逆转。反过来，该途径的晚期抑制和精氨酸通过精氨酸酶的催化作用可以促进伤口内的巨噬细胞功能。
Arginine can be metabolized by inflammatory cells through at least two pathways. One is an oxidative l-arginine deiminase (OAD) that results in the formation of citrulline and reactive nitrogen intermediates. The other is arginase, which determines the production of ornithine and urea. The temporal expression of these pathways in an experimental wound model (s.c. implanted polyvinyl alcohol sponges in the rat) was investigated by examining the concentrations of amino acids and of nitrite in fluids obtained from the sponges 6 h to 15 day after implantation. These analyses revealed two distinct periods during which the arginine concentration in the fluids was markedly below plasma levels. During the early period (less than 3 days after sponge implantation) wound fluid contained more citrulline and nitrite than at any other time, suggesting OAD activity. In contrast, ornithine accumulated in the fluids during the late decrease in arginine concentration that extended beyond day 3, during which time the wound fluid also contained a high arginase activity. This time-dependent expression of different pathways of arginine metabolism in wounds was confirmed in sponge cultures containing [guanido-14C]-l-arginine. Cells contained in sponges harvested less than 48 h after implantation metabolized labeled arginine mainly to labeled citrulline, whereas labeled urea was produced during culture of sponges harvested after this time. The low arginine content of wound fluid did not appear to be rate limiting for the expression of OAD in late sponges because no OAD activity was evidenced when 4 mM arginine was added to the cultures. These results indicate that the OAD pathway is expressed in this model predominantly during the early, polymorphonuclear leukocyte-predominant, phase of repair. At this time, the reactive nitrogen intermediates resulting from the metabolism of arginine may mediate some of the events characteristic of early inflammation, including microbiostasis, vasodilation, and inhibition/reversal of platelet aggregation. In turn, the late suppression of this pathway and the catabolism of arginine through arginase may promote macrophage function within wounds.