Adachi Y, Kindzelskii A L, Cookingham G, Shaya S, Moore E C, Todd R F, Petty H R
Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202, USA.
J Invest Dermatol. 1998 Aug;111(2):259-68. doi: 10.1046/j.1523-1747.1998.00311.x.
Having previously associated metabolic oscillations with cell locomotion, we hypothesized that patients with abnormalities in neutrophil trafficking may display aberrant intracellular oscillations. A pyoderma gangrenosum patient exhibiting aberrant leukocyte trafficking in vivo and skin ulceration without infection was identified. This patient's neutrophils constitutively overexpressed and clustered the leukocyte integrins CR3 and CR4 and failed to display appropriate integrin-to-GPI receptor interactions. Increased levels of tyrosine phosphorylation were observed. NAD(P)H oscillations, which are sinusoidal in normals, were chaotic with multiple frequency components in this patient's neutrophils. Normal cell shape and sinusoidal NAD(P)H oscillations were restored by providing a pulsed electric field to drive metabolic oscillations and by temperature reduction. N-acetyl-D-glucosamine disrupted CR3 clusters and sinusoidal NAD(P)H oscillations returned. Anecdotal reports suggest that local hypothermia is clinically useful for this patient. These data define the first metabolic oscillation-associated disease and suggest that pyoderma gangrenosum can be classified as a dynamical disease at the cellular level.
由于之前已将代谢振荡与细胞运动联系起来，我们推测中性粒细胞运输异常的患者可能会表现出异常的细胞内振荡。我们鉴定出一名坏疽性脓皮病患者，该患者在体内存在异常的白细胞运输且皮肤溃疡但无感染。该患者的中性粒细胞组成性地过度表达并聚集白细胞整合素CR3和CR4，且未能表现出适当的整合素与糖基磷脂酰肌醇（GPI）受体相互作用。观察到酪氨酸磷酸化水平升高。在正常人中呈正弦波的NAD（P）H振荡在该患者的中性粒细胞中呈混沌状态，具有多个频率成分。通过提供脉冲电场以驱动代谢振荡和降低温度，可恢复正常的细胞形态和正弦波状的NAD（P）H振荡。N-乙酰-D-葡萄糖胺破坏了CR3簇，正弦波状的NAD（P）H振荡恢复。轶事报告表明局部低温对该患者在临床上有用。这些数据定义了首例与代谢振荡相关的疾病，并表明坏疽性脓皮病可在细胞水平上归类为一种动态疾病。
