Upregulation of phagocyte-derived catecholamines augments the acute inflammatory response.
Upregulation of phagocyte-derived catecholamines augments the acute inflammatory response.
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DOI：
10.1371/journal.pone.0004414
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Ward, Peter A.
中科院分区：
文献类型：
--
作者：
Flierl, Michael A.;Rittirsch, Daniel;Nadeau, Brian A.;Sarma, J. Vidya;Day, Danielle E.;Lentsch, Alex B.;Huber-Lang, Markus S.;Ward, Peter A.
根据我们最近的报告，吞噬细胞（中性粒细胞，PMN和巨噬细胞）是新发现的儿茶酚胺来源，我们现在表明肾上腺素和去甲肾上腺素直接激活巨噬细胞中的NFκB，导致促炎细胞因子（TNFα，IL-1β，IL-6）的释放增加。使用了肾上腺完整（AD+）和肾上腺切除（ADX）啮齿动物，因为ADX动物极大地增强了吞噬细胞释放的儿茶酚胺，有助于我们理解吞噬细胞释放的儿茶酚胺的作用。从肾上腺切除大鼠中分离的吞噬细胞表现出增强的酪氨酸羟化酶和多巴胺-β-羟化酶表达，这两种酶是儿茶酚胺产生的关键酶，并表现出较高的去甲肾上腺素和肾上腺素基线分泌。在两种急性肺损伤（ALI）模型中研究了吞噬细胞衍生的儿茶酚胺上调的作用。吞噬细胞衍生的儿茶酚胺水平升高与急性炎症反应的加剧相关，如通过白蛋白血浆渗漏增加、肺中髓过氧化物酶含量增加、支气管肺泡灌洗液中促炎介质水平增加以及肺ICAM-1和VCAM-1表达升高所评估的。在肾上腺切除的大鼠中，ALI的发展增强，并且与α2-肾上腺素受体的参与有关，但与盐皮质激素或糖皮质激素受体的参与无关。总的来说，这些数据表明，儿茶酚胺是巨噬细胞的有效炎症激活剂，上调NFκB和这些细胞的进一步下游细胞因子产生。在肾上腺切除动物中（已用于进一步评估儿茶酚胺的作用），巨噬细胞中的儿茶酚胺生成酶和儿茶酚胺似乎代偿性增加，导致急性炎症反应通过α2-肾上腺素受体的参与而放大。
Following our recent report that phagocytic cells (neutrophils, PMNs, and macrophages) are newly discovered sources of catecholamines, we now show that both epinephrine and norepinephrine directly activate NFκB in macrophages, causing enhanced release of proinflammatory cytokines (TNFα, IL-1β, IL-6). Both adrenal-intact (AD+) and adrenalectomized (ADX) rodents were used, because ADX animals had greatly enhanced catecholamine release from phagocytes, facilitating our efforts to understand the role of catecholamines released from phagocytes. Phagocytes isolated from adrenalectomized rats displayed enhanced expression of tyrosine-hydroxylase and dopamine-β-hydroxylase, two key enzymes for catecholamine production and exhibited higher baseline secretion of norepinephrine and epinephrine. The effects of upregulation of phagocyte-derived catecholamines were investigated in two models of acute lung injury (ALI). Increased levels of phagocyte-derived catecholamines were associated with intensification of the acute inflammatory response, as assessed by increased plasma leak of albumin, enhanced myeloperoxidase content in lungs, augmented levels of proinflammatory mediators in bronchoalveolar lavage fluids, and elevated expression of pulmonary ICAM-1 and VCAM-1. In adrenalectomized rats, development of ALI was enhanced and related to α2-adrenoceptors engagement but not to involvement of mineralocorticoid or glucocorticoid receptors. Collectively, these data demonstrate that catecholamines are potent inflammatory activators of macrophages, upregulating NFκB and further downstream cytokine production of these cells. In adrenalectomized animals, which have been used to further assess the role of catecholamines, there appears to be a compensatory increase in catecholamine generating enzymes and catecholamines in macrophages, resulting in amplification of the acute inflammatory response via engagement of α2-adrenoceptors.
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影响因子：
3.6
作者：
Kradin, R;Rodberg, G;Leary, C
通讯作者：
Leary, C
影响因子：
2.9
作者：
Bergquist, J;Josefsson, E;Ewing, A
通讯作者：
Ewing, A
影响因子：
6
作者：
Czermak, BJ;Lentsch, AB;Ward, PA
通讯作者：
Ward, PA
DOI：
10.1073/pnas.91.26.12912
发表时间：
1994-12-20
影响因子：
11.1
作者：
BERGQUIST, J;TARKOWSKI, A;EWING, A
通讯作者：
EWING, A
影响因子：
15.9
作者：
Lentsch, AB;Shanley, TP;Ward, PA
通讯作者：
Ward, PA