Smith B L, Baumgarten R, Nielsen S, Raben D, Zeidel M L, Agre P
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Clin Invest. 1993 Oct;92(4):2035-41. doi: 10.1172/JCI116798.
Major phenotypic changes occur in red cell membranes during the perinatal period, but the underlying molecular explanations remain poorly defined. Aquaporin CHIP, the major erythroid and renal water channel, was studied in perinatal rats using affinity-purified anti-CHIP IgG for immunoblotting, flow cytometry, and immunofluorescence microscopy. CHIP was not detected in prenatal red cells but was first identified in circulating red cells on the third postnatal day. Most circulating red cells were positive for CHIP by the seventh postnatal day, and this proportion rose to nearly 100% by the 14th day. The ontogeny of red cell CHIP correlated directly with acquisition of osmotic water permeability and inversely with Arrhenius activation energy. Only minor alterations in the composition of red cell membrane lipids occurred at this time. Immunohistochemical analysis of perinatal kidneys demonstrated a major induction of CHIP in renal proximal tubules and descending thin limbs at birth, coincident with the development of renal concentration mechanisms. Therefore, water channels are unnecessary for oxygen delivery or survival in the prenatal circulation, however CHIP may confer red cells with the ability to rehydrate rapidly after traversing the renal medulla, which becomes hypertonic after birth.
围产期红细胞膜会发生重大的表型变化，但其潜在的分子机制仍不清楚。水通道蛋白CHIP是主要的红细胞和肾脏水通道，在围产期大鼠中进行了研究，使用亲和纯化的抗CHIP IgG进行免疫印迹、流式细胞术和免疫荧光显微镜检查。产前红细胞中未检测到CHIP，但在出生后第三天首次在循环红细胞中发现。到出生后第七天，大多数循环红细胞CHIP呈阳性，到第14天这一比例上升至近100%。红细胞CHIP的个体发生与渗透水通透性的获得直接相关，与阿累尼乌斯活化能呈负相关。此时红细胞膜脂质组成仅发生轻微变化。围产期肾脏的免疫组织化学分析表明，出生时肾近端小管和降支细段中CHIP大量诱导，这与肾脏浓缩机制的发育同时发生。因此，水通道对于产前循环中的氧气输送或生存并非必需，然而CHIP可能赋予红细胞在穿过出生后变为高渗的肾髓质后快速补水的能力。
