BACKGROUND & AIMS:
:The developing fetal and neonatal gastrointestinal (GI) tract is influenced by many growth factors, including epidermal growth factor (EGF), insulin-like growth factor (IGF), transforming growth factor (TGF), and erythropoietin (Epo). Granulocyte colony-stimulating factor (G-CSF), typically regarded as a hematopoietic growth factor, might also be included because it exists in high concentrations in amniotic fluid, colostrum, and human milk, and because granulocyte CSF receptors (G-CSF-R) are abundantly expressed on the villous enterocytes of the developing intestine. As a first step toward understanding whether the effects of G-CSF on the GI tract were local or systemic, we sought to determine whether recombinant human G-CSF (rhG-CSF) administered enterally to suckling mice, is absorbed into the circulation, and if so, whether the G-CSF-R is essential for this absorption. We enterally administered rhG-CSF to suckling mice, selecting a daily dose based on the amount of G-CSF normally swallowed by the fetus and neonate (3 ng), or in other mice, a dose of G-CSF 100 times larger (300 ng). Pups were tested at either 5-7 days of age, or at 14-16 days of age. C57BL/6 x 129SvJ mice were used. Some mice had a targeted null mutation in the G-CSF-R gene, producing a non-functional G-CSF-R protein. At intervals following the enteral G-CSF dosing, G-CSF concentrations in plasma were measured by specific ELISA. The bioavailability of G-CSF was invariably <1%, regardless of the dose of rhG-CSF given, the age of the pups, or whether they had a functional G-CSF-R. After enteral administration of rhG-CSF to suckling mice, only minimal quantities of G-CSF are absorbed into the circulation, and the G-CSF-R is not essential for this absorption.
背景与目标:
: 胎儿和新生儿胃肠道 (GI) 的发育受许多生长因子的影响,包括表皮生长因子 (EGF),胰岛素样生长因子 (IGF),转化生长因子 (TGF) 和促红细胞生成素 (Epo)。粒细胞集落刺激因子 (g-csf),通常被视为造血生长因子,也可能被包括在内,因为它以高浓度存在于羊水,初乳和人乳中,并且因为粒细胞CSF受体 (g-csf-R) 在发育中的肠道的绒毛状肠细胞上大量表达。作为了解g-csf对胃肠道的影响是局部还是全身的第一步,我们试图确定肠内施用给哺乳小鼠的重组人g-csf (rhG-CSF) 是否被吸收到循环中,如果是,g-csf-r是否对这种吸收至关重要。我们向哺乳小鼠肠内施用rhG-CSF,根据胎儿和新生儿通常吞咽的g-csf的量选择每日剂量 (3 ng),或者在其他小鼠中,g-csf的剂量大100倍 (300 ng)。幼崽在5-7天大或14-16天大时进行测试。使用C57BL/6 x 129SvJ小鼠。一些小鼠在g-csf-r基因中具有靶向的无效突变,产生无功能的g-csf-r蛋白。在肠内g-csf给药后的间隔内,通过特异性ELISA测量血浆中的g-csf浓度。G-csf的生物利用度总是 <1%,无论给予rhG-CSF的剂量、幼崽的年龄或它们是否具有功能性g-csf-r。向哺乳小鼠肠内施用rhG-CSF后,只有极少量的g-csf被吸收到循环中,而g-csf-R对于这种吸收不是必需的。