A Potential Role for Annexin 1 as a Physiologic Mediator of Glucocorticoid-Induced L-Selectin Shedding from Myeloid Cells1
A Potential Role for Annexin 1 as a Physiologic Mediator of Glucocorticoid-Induced L-Selectin Shedding from Myeloid Cells1
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膜联蛋白 1 作为糖皮质激素诱导的骨髓细胞 L-选择素脱落的生理调节剂的潜在作用1
作者：
H. Strausbaugh;S. Rosen
糖皮质激素可通过抑制中性粒细胞聚集到组织部位来抑制炎症反应。糖皮质激素对中性粒细胞发挥这种作用的详细机制尚不清楚。L-选择素是一种白细胞表面受体，参与中性粒细胞募集的几个步骤。最近，一些研究表明，全身治疗的动物和人类与糖皮质激素诱导中性粒细胞上的L-选择素表达减少，这表明炎症可能是负调控的一种机制。然而，当中性粒细胞在体外用糖皮质激素处理时，没有观察到对L-选择素表达的影响。因此，存在一个额外的调解人是合理的。在这项研究中，我们调查是否膜联蛋白1（ANX 1），公认的糖皮质激素的第二信使，可能是这样的调解人。我们发现ANX 1诱导外周血中性粒细胞和单核细胞L-选择素表达的剂量和时间依赖性降低，但对淋巴细胞没有影响。中性粒细胞L-选择素的损失是由于细胞表面金属蛋白酶（“脱落酶”）介导的脱落。使用细胞形状和β2整合素活化表位，我们表明ANX 1诱导的L-选择素脱落似乎在没有明显细胞活化的情况下发生。这些数据可能为进一步了解炎症反应下调的机制提供了基础。
Glucocorticoids can dampen inflammatory responses by inhibiting neutrophil recruitment to tissue sites. The detailed mechanism by which glucocorticoids exert this affect on neutrophils is unknown. L-selectin is a leukocyte cell surface receptor that is implicated in several steps of neutrophil recruitment. Recently, several studies have shown that systemic treatment of animals and humans with glucocorticoids induces decreased L-selectin expression on neutrophils, suggesting one mechanism by which inflammation may be negatively regulated. However, when neutrophils are treated in vitro with glucocorticoids, no effect on L-selectin expression is observed. Thus, the existence of an additional mediator is plausible. In this study, we investigate whether annexin 1 (ANX1), a recognized second messenger of glucocorticoids, could be such a mediator. We show that ANX1 induces a dose- and time-dependent decrease in L-selectin expression on both peripheral blood neutrophils and monocytes but has no effect on lymphocytes. The loss of L-selectin from neutrophils is due to shedding that is mediated by a cell surface metalloprotease (“sheddase”). Using cell shape and a β2 integrin activation epitope, we show that the ANX1-induced shedding of L-selectin appears to occur without overt cell activation. These data may provide the basis for further understanding of mechanisms involved in the down-regulation of inflammatory responses.
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膜联蛋白 I 和 II 与脂质 A 结合：可能在抑制内毒素中发挥作用。
DOI：
10.1042/bj3300067
发表时间：
1998
期刊：
The Biochemical journal
影响因子：
--
作者：
Eberhard,DA;Vandenberg,SR
通讯作者：
Vandenberg,SR
DOI：
10.1016/s0021-9258(17)36831-x
发表时间：
1994-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
N. Mukaida;M. Morita;Y. Ishikawa;N. Rice;S. Okamoto;T. Kasahara;K. Matsushima
通讯作者：
N. Mukaida;M. Morita;Y. Ishikawa;N. Rice;S. Okamoto;T. Kasahara;K. Matsushima
影响因子：
4.4
作者：
K. Ley;T. Tedder
通讯作者：
K. Ley;T. Tedder
影响因子：
6.4
作者：
ANDERSON, DC;SCHMALSTEIG, FC;SPRINGER, TA
通讯作者：
SPRINGER, TA
影响因子：
56.9
作者：
KISHIMOTO, TK;JUTILA, MA;BUTCHER, EC
通讯作者：
BUTCHER, EC