Chemoattractant receptor functions in human polymorphonuclear leukocytes are divergently altered by membrane fluidizers.

Chemoattractant receptor functions in human polymorphonuclear leukocytes are divergently altered by membrane fluidizers.
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人多形核白细胞中的趋化受体功能被膜流化剂不同程度地改变。

DOI:
10.1073/pnas.79.19.5906
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发表时间:
1982
影响因子:
11.1
通讯作者:
Synderman,R
Synderman,R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Yuli,I;Tomonaga,A;Synderman,R

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白细胞上的趋化因子受体启动几种细胞反应,包括趋化性、溶酶体酶分泌和O2-产生。后两种反应需要比趋化性所需的化学引诱物多大约10-100倍。我们确定了膜流化剂对寡肽fMet-Leu-Phe趋化因子受体在多形核白细胞上的结合特性和功能活性的影响。流化由脂肪醇诱导,并通过二苯基己三烯荧光偏振监测。低剂量的正丁醇(0.25%)和正戊醇(0.1%)是无毒的白细胞,但减少其二苯基己三烯诱导的极化,表明增加膜流动性。在这些醇剂量下,fMet-Leu-Phe受体的亲和力分别从Kd = 25.5 +/- 7.6 nM增强至Kd = 5.2 +/- 0.9 nM和Kd = 6.0 +/- 0.9 nM。趋化性也增加,如fMet-Leu-Phe的ED 50减少约1/3的因子所示,以及在0.25%丁醇或0.1%戊醇存在下最大迁移距离增加1.5倍。在相反的趋化性,醇抑制fMet-Leu-Phe刺激O2-生产的90%,虽然他们没有影响佛波醇12-肉豆蔻酸酯13-乙酸酯诱导的O2-生产。溶菌酶的分泌也受到抑制。因此,fMet-Leu-Phe受体的亲和力可以通过膜流化剂来调节。由醇类诱导的受体的较高亲和力状态在转导趋化信号方面更有效,但在介导O2-产生或分泌方面不足。因此,趋化因子受体的各种生物活性的转导机制是异质的,并且可以通过膜流化剂进行差异化操纵。
The chemotactic factor receptor on leukocytes initiates several cellular responses including chemotaxis, lysosomal enzyme secretion, and O2- production. The latter two responses require approximately 10-100 times more chemoattractant than is required for chemotaxis. We determined the effects of membrane fluidizers on the binding characteristics and the functional activities of the oligopeptide fMet-Leu-Phe chemotactic factor receptor on polymorphonuclear leukocytes. Fluidization was induced by aliphatic alcohols and monitored by diphenylhexatriene fluorescence polarization. Low doses of n-butanol (0.25%) and n-pentanol (0.1%) were nontoxic to the leukocytes yet reduced their diphenylhexatriene-induced polarization, indicating increased membrane fluidity. At these doses of alcohols, the affinity of the fMet-Leu-Phe receptor was enhanced from Kd = 25.5 +/- 7.6 nM to Kd = 5.2 +/- 0.9 nM and Kd = 6.0 +/- 0.9 nM, respectively. Chemotaxis was also increased, as indicated by the decrease, by a factor of approximately 1/3 in the ED50 for fMet-Leu-Phe, as well as by a 1.5-fold increase in the maximal distance of migration in the presence of 0.25% butanol or 0.1% pentanol. In contrast to chemotaxis, the alcohols depressed fMet-Leu-Phe stimulation of O2- production by 90% although they had no effect on phorbol 12-myristate 13-acetate-induced O2- production. Secretion of lysozyme was also inhibited. Thus, the affinity of the fMet-Leu-Phe receptor can be modulated by membrane fluidizers. The higher affinity state of the receptor induced by the alcohols is more efficient in transducing chemotactic signals but is deficient in mediating O2- production or secretion. Thus, the transduction mechanisms for the various biological activities of the chemotactic factor receptor are heterogeneous and can be differentially manipulated by membrane fluidizers.
DOI: --
发表时间: 1981
期刊:
影响因子: --
作者:
S. B. Brown
通讯作者: S. B. Brown
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DOI: --
发表时间: 1980
期刊:
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作者:
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DOI: --
发表时间: 1978
期刊:
影响因子: --
作者:
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