The central role of PAF in necrotizing enterocolitis development.
The central role of PAF in necrotizing enterocolitis development.
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PAF 在坏死性小肠结肠炎发展中的核心作用。
DOI：
10.1007/978-1-4899-1813-0_56
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发表时间：
1997
影响因子：
--
通讯作者：
J. Johnston
中科院分区：
文献类型：
--
作者：
K. Muguruma;P. Gray;L. Tjoelker;J. Johnston
我们讨论了有关NEC发展的两个关键问题。1)为什么新生儿肠道特别容易坏死？2）PAF在NEC的发展中是否起着关键作用？我们发现新生儿的肠组织对从头途径的乙酰转移酶具有最高的比活性。这表明该组织合成PAF的高能力可能有助于新生儿坏死在该组织中更普遍的事实。我们以前曾报道，地塞米松降低活性的乙酰辅酶A：溶血PAF乙酰转移酶在肝脏和脾脏。该激素还引起血浆PAF-乙酰水解酶活性的增加和各种巨噬细胞PAF-乙酰水解酶分泌的增加。因此，糖皮质激素对NEC预防的有益作用可能是由于PAF乙酰水解酶增加引起的PAF失活增加以及PAF合成减少。我们目前正在研究糖皮质激素对乙酰辅酶A：烷基-溶血-sn-甘油-3-磷酸乙酰转移酶的影响。报告的研究中，NEC的预防静脉输注重组PAF-乙酰水解酶提供了进一步的文件PAF在NEC的发展的重要性。地塞米松保护所需的PAF-乙酰水解酶的比活性相似。这一发现提示地塞米松引起针对NEC的完全保护的机制可能是通过增加血浆活性介导的。已经提出了其他机制，例如促进小肠的成熟。如所讨论的，其他因素如缺氧、内毒素、TNF α和肠内喂养被认为是NEC发展的促成因素。众所周知，其中许多因素和程序都会增加阵发性房颤。我们已经提出了一种机制来解释由LPS、TNF α和白细胞介素引起的PAF形成的增加，即巨噬细胞对PAF-AH的分泌的抑制。我们以前的报告涉及的机制，在预防NEC的糖皮质激素和报告的发现，人重组PAF-乙酰水解酶可以防止NEC提供了进一步的支持，PAF在NEC的发展中的核心作用。此外，在新生儿肠道中存在高PAF生物合成活性提供了关于为什么该组织对该疾病高度易感的解释。
We have addressed two critical questions concerning NEC development. 1) Why is the neonatal intestine particularly susceptible to necrosis? and 2) Does PAF play a critical role in NEC development? We have found that intestinal tissue of the newborn has the highest specific activity for the acetyltransferase of the de novo pathway. It is suggested that the high capacity of this tissue to synthesize PAF may contribute to the fact that the necrosis of the newborn is more prevalent in this tissue. We have previously reported that dexamethasone lowers the activity of acetyl-CoA:lyso-PAF acetyltransferase in liver and spleen. This hormone also cause an increase in plasma PAF-acetylhydrolase activity and an increased secretion of PAF-acetylhydrolase by various macrophages. It would, therefore, appear that the beneficial effects of glucocorticoids on the prevention of NEC may be due to both increased inactivation of PAF as caused by the increase in PAF-acetylhydrolase as well as a decrease in PAF synthesis. We are presently investigating the effect of glucocorticoids on acetyl-CoA: alkyl-lyso-sn-glycero-3-phosphate acetyltransferase. The reported studies in which NEC was prevented by intravenous infusion of recombinant PAF-acetylhydrolase provides further documentation as to the importance of PAF in the development of NEC. The specific activity of PAF-acetylhydrolase required for protection by dexamethasone was similar. This finding would be suggestive of the fact that the mechanisms by which dexamethasone causes a complete protection against NEC may be mediated by increasing the plasma activity. Other mechanisms have been proposed such as facilitating the maturation of the small bowel. As discussed, other factors such as hypoxia, endotoxins, TNF alpha, and enternal feeding have been suggested to be contributing agents of NEC development. Many of these factors and procedures are known to increase in PAF. We have suggested a mechanism to explain the increase in PAF formation as caused LPS, TNF alpha, and interleukins being the inhibition of the secretion of PAF-AH by macrophages. Our previous reports on the mechanisms involve in the prevention of NEC by glucocorticoids and the reported findings that human recombinant PAF-acetylhydrolase can prevent NEC provide further support for a central role for PAF in NEC development. Furthermore, the presence of a high PAF biosynthetic activity in the neonatal intestine affords an explanation as to why this tissue is highly susceptible to this disease.
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影响因子：
9.8
作者：
Hisashi Narahara;Yuichi Nishioka;John M. Johnston
通讯作者：
Hisashi Narahara;Yuichi Nishioka;John M. Johnston
大鼠组织中血小板活化因子乙酰转移酶活性的激素调节。
影响因子：
3.9
作者：
Ihara,Y;Frenkel,RA;Johnston,JM
通讯作者：
Johnston,JM
影响因子：
2.1
作者：
Toyoshima,K;Narahara,H;Furukawa,M;Frenkel,RA;Johnston,JM
通讯作者：
Johnston,JM
牛奶中存在血小板激活因子乙酰水解酶。
影响因子：
6.5
作者：
Furukawa,M;Narahara,H;Yasuda,K;Johnston,JM
通讯作者：
Johnston,JM