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Effects of IgM from rheumatic fever patients on intracellular calcium levels of neonatal rat cardiac myocytes.

机译:风湿热患者的IgM对新生大鼠心肌细胞内钙水平的影响。

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Rheumatic fever (RF), a potential sequela of Streptococcus pyogenes pharyngitis, sometimes results in myocarditis and heart failure. Antibodies have been implicated in the pathogenesis of RF and anti-cardiac myosin antibody levels are elevated in RF patients. Since myocarditis is associated with altered cardiomyocyte calcium transients it was of interest to determine the direct effects of RF patient antibodies on calcium transients in cultured myocytes. RF patient polyclonal IgM treatment caused increased calcium retention by neonatal rat heart cells in vitro as determined with isotopically labeled calcium. Therefore, to further characterize this finding, calcium transients were evaluated by real time fluorescence spectroscopy and deconvolution imaging. RF patient polyclonal IgM produced increased calcium retention during the relaxation stage of the contraction cycle leading to a slowing of contraction rate, disorganized calcium transients, and eventual tetany. In contrast, calcium transient studies ofcardiomyocytes following treatment with monoclonal anti-myosin antibodies revealed declining intracellular calcium levels, accompanied by disorganized transients and tetany. Treatment with both antibodies led to myocyte dysfunction and these novel findings suggest a role for antibodies in the pathogenesis of the myocarditis associated with rheumatic carditis.
机译:风湿热(RF)是化脓性链球菌咽炎的潜在后遗症,有时会导致心肌炎和心力衰竭。抗体与RF的发病机理有关,RF患者的抗心肌肌球蛋白抗体水平升高。由于心肌炎与心肌细胞钙瞬变改变有关,因此确定RF患者抗体对培养的心肌细胞钙瞬变的直接作用是很有意义的。 RF患者多克隆IgM治疗可导致新生大鼠心脏细胞的钙保留增加,这是通过同位素标记的钙确定的。因此,为进一步表征该发现,可通过实时荧光光谱和去卷积成像评估钙瞬变。 RF患者多克隆IgM在收缩周期的松弛阶段产生的钙保留增加,导致收缩率减慢,钙瞬变紊乱和最终发生手足抽搐。相反,在用单克隆抗肌球蛋白抗体治疗后心肌细胞的钙瞬变研究显示,细胞内钙水平下降,伴有混乱的瞬变和强直性。两种抗体的治疗均导致肌细胞功能障碍,这些新发现提示抗体在与风湿性心脏病相关的心肌炎的发病机理中具有重要作用。

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