{"title":"Altered intracellular calcium signalling after PAF stimulations in polymorphonuclear leukocytes from asthmatic patients","authors":"P. Bialasiewicz, D. Nowak, M. Krol, A. Antczak","doi":"10.1016/S0929-7855(97)00018-7","DOIUrl":null,"url":null,"abstract":"<div><p>Platelet activating factor (PAF), a potent lipid mediator, has been implicated in the pathogenesis of airways inflammation in bronchial asthma. Binding of PAF to its receptor (Nakamura et al., 1991) leads to changes of intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub><em>i</em></sub>) that is crucial to cell activation. Therefore, the aim of our study was to investigate whether PMNL of asthmatic patients stimulated with PAF(10<sup>−7</sup> M) differ in relation to changes of [Ca<sup>2+</sup>]<sub><em>i</em></sub> from cells of healthy subjects. PMNL from asthmatic patients revealed attenuated first response to PAF stimulation—increase in [Ca<sup>2+</sup>]<sub><em>i</em></sub> (A[Ca<sup>2+</sup>]<sub><em>i</em></sub>) was 1.3-fold lower in cells of asthmatics (<em>P</em> < 0.05) versus PMNL of healthy subjects. As determined in experiments with low extracellular calcium concentration, Ca<sup>2+</sup> release from internal stores tended to be increased in asthmatics and hence the difference in total Ca<sup>2+</sup> response was related to decrease in Ca<sup>2+</sup> influx. Thus the contribution of Ca<sup>2+</sup> from internal stores to the total first Ca<sup>2+</sup> response upon PAF stimulation was two-fold higher (58 ± 18 vs. 29 ± 8%, <em>P</em> < 0.001) in PMNL of asthmatics compared with healthy subjects. Two subsequent Ca<sup>2+</sup> responses evoked by stimulations with the agonist in 1 mM Ca<sup>2+</sup> buffer did not differ between study groups. In low Ca<sup>2+</sup> buffer PMNL of 50% of asthmatics responded to the second stimulation while cells of healthy subjects remained unresponsive. The altered Ca<sup>2+</sup> responses in PMNL of asthmatic subjects may reflect previous contact with mediator(s) that occur in vivo which may be at least partially explained by the phenomenon of down regulation reported for PAF receptor upon cell stimulation.</p></div>","PeriodicalId":79347,"journal":{"name":"Journal of lipid mediators and cell signalling","volume":"17 1","pages":"Pages 21-30"},"PeriodicalIF":0.0000,"publicationDate":"1997-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0929-7855(97)00018-7","citationCount":"5","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of lipid mediators and cell signalling","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0929785597000187","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 5
Abstract
Platelet activating factor (PAF), a potent lipid mediator, has been implicated in the pathogenesis of airways inflammation in bronchial asthma. Binding of PAF to its receptor (Nakamura et al., 1991) leads to changes of intracellular Ca2+ concentration ([Ca2+]i) that is crucial to cell activation. Therefore, the aim of our study was to investigate whether PMNL of asthmatic patients stimulated with PAF(10−7 M) differ in relation to changes of [Ca2+]i from cells of healthy subjects. PMNL from asthmatic patients revealed attenuated first response to PAF stimulation—increase in [Ca2+]i (A[Ca2+]i) was 1.3-fold lower in cells of asthmatics (P < 0.05) versus PMNL of healthy subjects. As determined in experiments with low extracellular calcium concentration, Ca2+ release from internal stores tended to be increased in asthmatics and hence the difference in total Ca2+ response was related to decrease in Ca2+ influx. Thus the contribution of Ca2+ from internal stores to the total first Ca2+ response upon PAF stimulation was two-fold higher (58 ± 18 vs. 29 ± 8%, P < 0.001) in PMNL of asthmatics compared with healthy subjects. Two subsequent Ca2+ responses evoked by stimulations with the agonist in 1 mM Ca2+ buffer did not differ between study groups. In low Ca2+ buffer PMNL of 50% of asthmatics responded to the second stimulation while cells of healthy subjects remained unresponsive. The altered Ca2+ responses in PMNL of asthmatic subjects may reflect previous contact with mediator(s) that occur in vivo which may be at least partially explained by the phenomenon of down regulation reported for PAF receptor upon cell stimulation.
血小板活化因子(PAF)是一种有效的脂质介质,与支气管哮喘气道炎症的发病机制有关。PAF与其受体的结合(Nakamura et al., 1991)导致细胞内Ca2+浓度([Ca2+]i)的变化,这对细胞活化至关重要。因此,我们的研究目的是探讨哮喘患者在PAF(10−7 M)刺激下的PMNL是否与健康受试者细胞中[Ca2+]i的变化有关。哮喘患者的PMNL显示对PAF刺激的第一反应减弱-哮喘患者细胞中[Ca2+]i (A[Ca2+]i)的增加降低了1.3倍(P <0.05)与健康受试者PMNL比较。正如在低细胞外钙浓度的实验中所确定的那样,哮喘患者体内Ca2+释放倾向于增加,因此总Ca2+反应的差异与Ca2+内流的减少有关。因此,在PAF刺激下,来自内部储存的Ca2+对总第一次Ca2+反应的贡献高出两倍(58±18 vs. 29±8%),P <0.001),哮喘患者PMNL与健康人比较。在1 mM Ca2+缓冲剂中激动剂刺激引起的两个随后的Ca2+反应在研究组之间没有差异。在低Ca2+缓冲中,50%的哮喘患者的PMNL对第二次刺激有反应,而健康受试者的细胞则没有反应。哮喘受试者PMNL中Ca2+反应的改变可能反映了先前与体内介质的接触,这可能至少部分地解释了细胞刺激时PAF受体下调的现象。