Neuropeptide-mediated regulation of hapten-specific IgE responses in mice II. Mechanisms of substance P-mediated isotype-specific suppression of BPO-specific IgE antibody-forming cell responses induced in vitro

Previous studies in our laboratory have shown that substance P (SP), injected into benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) sensitized mice at the peak of the benzylpenicilloyl (BPO)-specific IgE response, suppressed these responses in isotype-specific fashion within 48 h. These studies also showed that SP, but not neurotensin (NT), serotonin (5-HT), somatostatin (SOM) or gastrin, suppressed BPO-specific memory IgE antibody-forming cell (AFC) responses induced in vitro, also in isotype-specific fashion. To investigate the mechanisms by which SP suppressed BPO-specific IgE AFC responses were induced in vitro, these responses were induced by culturing spleen cells from BPO-KLH sensitized mice for 5 days with BPO-KLH with or without whole SP, amino terminal SP (SP 1–4: Arg-Lys-Pro-Lys), or carboxy terminal SP (SP 8–11: Phe-Gly-Leu-Met). In some experiments, the SP receptor antagonist (d-Pro², d-Phe⁷, d-Trp⁹)-SP (d-SP) was included in culture. In other experiments anti-interferon monoclonal antibody (anti-IFNγ mAb) was included in culture. Whole SP and SP 8–11, but not SP 1–4, suppressed BPO-specific IgE AFC responses induced in vitro. The suppression obtained was IgE isotype-specific and dose-dependent. Inclusion of SP receptor antagonist (d-Pro², d-Phe⁷, d-Trp⁹)-SP inhibited suppression of BPO-specific memory IgE AFC responses by SP or SP 8–11. The SP-mediated suppression of BPO-specific memory IgE responses appeared to involve interferon gamma (IFNγ).     

动态观察脑出血患者血浆神经肽Y、神经降压素和胃动素的临床意义

动态观察脑出血患者血浆神经肽Y(NPY)、神经降压素(NT)和胃动素(MTL)的水平 变化,探讨其临床意义。方法采用放射免疫方法测定了46例脑出血患者及28例健康成人血浆NPY、NT及MTL的含量。结果脑出血患者血浆NPY、NT及MTL水平均明显高于对照组(P<0.001,P<0.01,P<0.01)。发病24h内即显著升高,NPY在4～7d、NT和MTL在1～3d达高峰,8～15d三者均开始下降,15d后仍在较高水平。重症患者NPY水平显著高于轻型和中型,中、重型患者NT水平显著高于轻型。大面积出血NPY、NT及MTL水平均高于小面积出血。伴发病积分≥6分者高于积分<6分者。伴上消化道出血者显著高于不伴上消化道出血者。结论NPY、NT及MTL参与了脑出血的发生及病理生理过程     

Multifactorial control of pituitary hormone secretion: the "wheels" of the brain

An attempt is made to deal with the complexity of the nerve fibers in the median eminence. Visual aids are presented in the shape of "wheels" that depict a dynamic interplay of neurochemicals which result in the release of hormones from the anterior pituitary gland. The multiplicity of neurochemicals in the median eminence is perceived to be responsible for the integrated control of pituitary hormone releasing factors.     

Brain-gut neuropeptides and the limitation of ethanol consumption

Recent studies have clearly shown powerful control of ingestive behavior by certain peptides known to be present in both brain and gut tissues. These "brain-gut neuropeptides" are thought to constitute endogenous factors responsible for the normal regulation of food intake. This review explores the potential for a role of these peptides in the limitation of ethanol intake, which shares several features with the control of food intake. The putative satiety role of the neuropeptides cholecystokinin and bombesin, and other brain-gut peptides is briefly described. The conclusion that voluntary ethanol intake is partially controlled as a function of the energy ethanol provides, and the rate of its utilization, is illustrated with data from recent studies of rat and hamster ethanol consumption. The possibility of neuropeptide influence on ethanol intake is presented in light of new findings that cholecystokinin and bombesin inhibit ethanol consumption in the rat. If neuropeptides are demonstrated to modulate ethanol intake by eliciting satiety, this information may be useful in the identification and understanding of the endogenous factors which regulate human alcohol intake, and will suggest possible peptide-based therapeutic interventions for control of alcohol abuse and alcoholism.     

Vasoactive intestinal peptide regulates osteoclast activity via specific binding sites on both osteoclasts and osteoblasts

Clinical and experimental observations, together with immunohistochemical findings, suggest that neuro-osteogenic interactions may occur in the skeleton. In this study, we have examined the effect of vasoactive intestinal peptide (VIP), one of the neuropeptides present in bone, on the activity of the bone-resorbing osteoclast. Effects on bone resorption were assessed by counting the number of pits formed by rat osteoclasts incubated on devitalized slices of bovine cortical bone. Under conditions with an initially sparse density of stromal cells/osteoblasts, VIP caused a rapid cytoplasmic contraction and decreased motility of osteoclasts. This was coupled with a decrease in the number of resorption lacunae and a decrease in the total area resorbed by the osteoclasts in 48-h cultures. Time-course experiments revealed that the inhibitory effects on contraction and motility were transient and that the cells gradually regained their activity, such that, when culture time was prolonged to 120 h, a stimulatory effect by VIP on bone resorption was observed. When osteoclasts were incubated on bone slices, in the presence of an initially large number of stromal cells/osteoblasts, VIP treatment increased the number of resorption pits and total bone area resorbed in 48-h cultures. Using atomic force microscopy, we provide direct evidence that both osteoclasts and stromal cells/osteoblasts bind VIP. Also, VIP was shown to cause a rapid rise of intracellular calcium in osteoclasts and in a proportion (20%) of stromal cells/osteoblasts. Taken together, these data suggest that differentiated osteoclasts are equipped with receptors for VIP that are linked to a transient inhibition of osteoclast activity and, in addition, that stromal cells/osteoblasts have VIP receptors coupled to a delayed stimulation of osteoclastic resorption.     

肥大细胞在小鼠佐剂性关节炎疼痛中的作用及其机制研究

目的:探讨肥大细胞在完全弗氏佐剂(CFA)诱导的小鼠佐剂性关节炎(AA)疼痛中的作用。方法:实验分为4组:正常对照组(control组)、AA模型组(model组)、AA模型+色甘酸钠(CS)组(CS组)和AA模型+肥大细胞缺失组(W-4Bao组)。每组6只小鼠,前3组均为健康雌性C57BL/6小鼠,W-4Bao组为肥大细胞缺乏的KitW-4Bao小鼠。除control组注射生理盐水外,其他各组小鼠右后足底皮下注射CFA构建慢性AA疼痛模型;CS组于致炎1 d后开始腹腔注射CS(20 mg/kg),其它各组给予等体积生理盐水,每日1次,连续给药14 d。分别于致炎第0、1、3、7、10和14天测量小鼠足掌厚度、机械刺激缩爪反应阈值(PWT)和热刺激缩爪反应潜伏期(PWL)。14 d后获取各组小鼠踝关节组织,组织切片进行HE和甲苯胺蓝染色,ELISA法检测踝关节组织中组胺(histamine)、类胰蛋白酶(tryptase)、P物质(SP)和降钙素基因相关肽(CGRP)的浓度。结果:小鼠致炎1 d后,与control组相比,model组小鼠右后足炎症表现明显,PWT和PWL显著降低(P&...     

大鼠肾上腺的NADPH,NPY,CGRP,SP,c—fos细胞化学特性

目的 探讨肾上腺内分泌组织和神经组织的双重组织学特性。方法 组织化学和免疫组织化学技术,在光学显微下观察ＮＡＤＰＨ、ＮＰＹ、ＣＧＲＰ、ＳＰ、ｃ－ｆｏｓ在大鼠肾上腺的分布。结果 肾上腺皮质分布有ＮＰＹ阳性神经细胞和神经纤维、ＣＧＲＰ阳性神经纤维;肾上腺髓质分布有ＮＡＤＰＨ－ｄ阳性神经细胞和神经纤维、ＣＧＲＰ阳性神经纤维、ＳＰ阳性神经纤维、ｃ－ｆｏｓ阳性神经细胞和神经纤维。肾上腺皮质球状带、网状带、束状带细胞均ＮＡＤＰＨ－ｄ阳性,髓质部分嗜铬细胞ＮＡＤＰＨ－ｄ阳性,部分嗜铬细胞ＮＰＹ阳性,部分嗜铬细胞ＣＧＲＰ阳性,部分嗜铬细胞ＳＰ阳性。结论 大鼠肾上腺接受广泛的非经典递质的神经支配,特别是肽能神经支配的肾上腺实质细胞及髓质嗜铬细胞,能分泌多种神经肽物质。提示肾上腺的内分泌活动不仅受到复杂的神经调节而且也受到自身的活     

多发伤后β-内腓肽和细胞粘附分子表达变化及临床意义

目的：探讨多发伤病人血清β－ｅｎｄ及外周血多形核粒细胞（ＰＭＮｓ）ＣＤ１８、ＣＤ５４表达变化。方法：使用放免分析技术和流式细胞术分别检测６５例多发伤伤员入院时、伤后１、３、７天血清皮质醇、β－ｅｎｄ浓度和ＰＭＮｓ上ＣＤ１８、ＣＤ５４的平均荧光通道（ＭＦＣ）变化，１３例健康志愿者为对照组。结果：创伤病人血清皮质醇浓度在伤后２４小时内较对照组高（Ｐ＜０．００１），但创伤组间无差异；β－ｅｎｄ浓度入院时     

The distributions and coexistence of peptides in nerve fibres of large bowel affected by Hirschsprung's disease

The distributions of nerve fibres immunoreactive for the peptides calcitonin gene-related peptide (CGRP), enkephalin (ENK), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP), and vasoactive intestinal peptide (VIP) and the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) were studied in healthy colon and samples of ganglionic and aganglionic colon from cases of proven Hirschsprung's disease. Studies of coexistence of reactivities in nerve fibres were performed to predict the possible origins of fibres that are found in the aganglionic bowel, e. g., from sensory or sympathetic ganglia. The muscularis externa of the ganglionic colon contained many nerve fibres immunoreactive for ENK, SP, and VIP, fewer for NPY, and only rare fibres reactive for CGRP, SOM, or TH. In ganglionic colon reactivities for SP and ENK coexisted in nerve fibres in the muscularis externa but in aganglionic colon no ENK immunoreactivity was found and most SP fibres were double-labelled with CGRP reactivity, indicating their probable sensory nature. Abnormally increased numbers of somatostatin-reactive fibres and noradrenergic fibres (marked by TH) were noted in the external muscle, but no coexistence was seen between these reactivities and only a small proportion of the noradrenergic fibres in the muscle showed NPY reactivity although almost all around blood vessels did. Many fibres in the diseased segment had coexistence of NPY and VIP reactivities; these may arise from more orally located intrinsic cell bodies or from pelvic parasympathetic ganglia. In the mucosa of aganglionic colon there was a striking lack of SP-reactive fibres while other fibre types were often normal in number. It is concluded that nerve fibres from sensory ganglia, sympathetic ganglia, nerve cells located more oral in the ganglionated part, and possibly from pelvic parasympathetic ganglia invade the aganglionic bowel in Hirschsprung's disease.