PDF(Pubmed)
Abstract：
UNASSIGNED: Symptoms in patients with systemic mastocytosis (SM) are associated with an increase in mast cell burden and release of mast cell-derived mediators. The most frequent presentation of SM is indolent SM (ISM), with moderate symptoms and prognosis. Basophil numbers in these patients are generally normal. However, when examining basophil activation in patients with ISM, we noted an abnormal response to N-formylmethione-leucyl-phenylalanine (fMLP).
UNASSIGNED: Our aim was to compare basophil responsiveness to fMLP and anti-IgE in healthy volunteers and patients with ISM and relate the findings to fMLP receptor (FPR) expression.
UNASSIGNED: Basophils isolated from peripheral blood of 15 patients with ISM and 14 healthy volunteers were stimulated with fMLP or anti-IgE. CD63 expression to assess basophil activation and expression of FPRs were assessed by flow cytometry.
UNASSIGNED: Baseline expression of CD63 on basophils was similar between the healthy volunteers and patients with ISM. fMLP induced higher expression of CD63 on basophils from patients with ISM, whereas responses to anti-IgE were similar between groups. Basophils from patients with ISM also had higher fMLP1 receptor (FPR1) expression, wheresas FPR2 and FPR3 were not detected. fMLP blocked the binding of anti-FPR1 antibody to FPR1, consistent with the conclusion that fMLP signals through FPR1.
UNASSIGNED: Level of fMLP-induced basophil activation is higher in patients with ISM, which is associated with an increase in FPR1 expression. Further investigation is needed to determine why FPR1 expression is elevated, whether such expression might serve as an additional surrogate marker in the diagnosis of ISM, and whether enhanced responses of basophils to fMPL might have some relationship to unexplained episodes of mediator release.
UNASSIGNED: Our aim was to compare basophil responsiveness to fMLP and anti-IgE in healthy volunteers and patients with ISM and relate the findings to fMLP receptor (FPR) expression.
UNASSIGNED: Basophils isolated from peripheral blood of 15 patients with ISM and 14 healthy volunteers were stimulated with fMLP or anti-IgE. CD63 expression to assess basophil activation and expression of FPRs were assessed by flow cytometry.
UNASSIGNED: Baseline expression of CD63 on basophils was similar between the healthy volunteers and patients with ISM. fMLP induced higher expression of CD63 on basophils from patients with ISM, whereas responses to anti-IgE were similar between groups. Basophils from patients with ISM also had higher fMLP1 receptor (FPR1) expression, wheresas FPR2 and FPR3 were not detected. fMLP blocked the binding of anti-FPR1 antibody to FPR1, consistent with the conclusion that fMLP signals through FPR1.
UNASSIGNED: Level of fMLP-induced basophil activation is higher in patients with ISM, which is associated with an increase in FPR1 expression. Further investigation is needed to determine why FPR1 expression is elevated, whether such expression might serve as an additional surrogate marker in the diagnosis of ISM, and whether enhanced responses of basophils to fMPL might have some relationship to unexplained episodes of mediator release.
摘要：
■全身性肥大细胞增多症（SM）患者的症状与肥大细胞负荷增加和肥大细胞衍生介质的释放有关。SM最常见的是惰性SM(ISM)，具有中度症状和预后。这些患者的嗜碱性粒细胞数量通常正常。然而,当检查ISM患者的嗜碱性粒细胞激活时，我们注意到对N-甲酰甲酮-亮氨酰-苯丙氨酸（fMLP）的异常反应。
■我们的目的是比较健康志愿者和ISM患者中嗜碱性粒细胞对fMLP和抗IgE的反应性，并将发现与fMLP受体（FPR）表达相关。
■从15名ISM患者和14名健康志愿者的外周血中分离的嗜碱性粒细胞用fMLP或抗IgE刺激。通过流式细胞术评估CD63表达以评估嗜碱性粒细胞活化和FPR的表达。
■健康志愿者和ISM患者嗜碱性粒细胞上CD63的基线表达相似。fMLP诱导ISM患者嗜碱性粒细胞上CD63的高表达，而对抗IgE的反应在组间相似。来自ISM患者的嗜碱性粒细胞也有较高的fMLP1受体（FPR1）表达，未检测到FPR2和FPR3。fMLP阻断抗FPR1抗体与FPR1的结合,与fMLP通过FPR1发信号的结论一致。
■在ISM患者中，fMLP诱导的嗜碱性粒细胞活化水平更高，这与FPR1表达的增加有关。需要进一步研究以确定FPR1表达升高的原因，这种表达是否可以作为ISM诊断的额外替代标记，以及嗜碱性粒细胞对fMPL的增强反应是否可能与无法解释的介体释放发作有关。
■我们的目的是比较健康志愿者和ISM患者中嗜碱性粒细胞对fMLP和抗IgE的反应性，并将发现与fMLP受体（FPR）表达相关。
■从15名ISM患者和14名健康志愿者的外周血中分离的嗜碱性粒细胞用fMLP或抗IgE刺激。通过流式细胞术评估CD63表达以评估嗜碱性粒细胞活化和FPR的表达。
■健康志愿者和ISM患者嗜碱性粒细胞上CD63的基线表达相似。fMLP诱导ISM患者嗜碱性粒细胞上CD63的高表达，而对抗IgE的反应在组间相似。来自ISM患者的嗜碱性粒细胞也有较高的fMLP1受体（FPR1）表达，未检测到FPR2和FPR3。fMLP阻断抗FPR1抗体与FPR1的结合,与fMLP通过FPR1发信号的结论一致。
■在ISM患者中，fMLP诱导的嗜碱性粒细胞活化水平更高，这与FPR1表达的增加有关。需要进一步研究以确定FPR1表达升高的原因，这种表达是否可以作为ISM诊断的额外替代标记，以及嗜碱性粒细胞对fMPL的增强反应是否可能与无法解释的介体释放发作有关。
