免疫细胞内源性儿茶酚胺的免疫调节作用

机体内儿茶酚胺（catecholamines,CAs）包括去甲肾上腺素（norepinephrine,NE）、肾上腺素（epinephrine,E）和多巴胺（dopamine,DA）。CAs由神经元和内分泌细胞合成和分泌,其主要功能是调节心血管、呼吸和消化等内脏活动。近三十年来的研究说明,CAs也参与调控机体的免疫功能,但CAs的这种免疫调节作用一般视为神经和内分泌系统调节的介导作用。然而,近年来的研究发现,免疫细胞也能合成CAs,这是对传统观念的一种补充和提高。免疫细胞内存在经典的CAs代谢途径,既有合成CAs的酪氨酸羟化酶（tyrosine hydroxylase,TH）又有降解CAs的单胺氧化酶（monoamine oxidase,MAO）和儿茶酚氧位甲基移位酶（catechol-O-methyl transferase,COMT）。免疫细胞合成的内源性CAs可以调控细胞的增殖、分化、凋亡和细胞因子生成等多种免疫功能。CAs的这些作用可能主要通过自分泌或旁分泌途径作用于免疫细胞上相应受体和细胞内环磷酸腺苷（cyclicAMP,cAMP）实现。细胞内氧化应激机制可能也参与免疫细胞内源性CAs的免疫调节作用。此外,一些自身免疫性疾病如多发性硬化、风湿性关节炎可能也与免疫细胞内CAs的代谢异常有关。上述发现不仅为免疫系统有可能成为除神经和内分泌系统以外的第三个CA能系统提供了证据,而且为免疫系统内源性CAs的功能意义拓展了认识。     

鱼类细胞因子研究进展

免疫系统是指机体识别和消除异物的防卫系统,主要功能是防御和维护机体自身稳定。鱼类免疫系统包括细胞免疫和体液免疫;细胞因子(Cytokine)是其中重要的组成部分。细胞因子是一类由免疫细胞和非特异性免疫细胞合成或分泌的小分子多肽物质,具有调节多种细胞生理功能的作用。在一般状况下,细胞因子的分泌量很低,或处于失活状态;但在机体的免疫细胞或组织受到刺激发生新的基因转录后,其含量将会大幅度上升,并识别细胞上高亲和性的表面受体,以协同形式结合其他的细胞因子或者抗病毒分子发挥生物学效应,发挥免疫调节作用。       

骨骼肌的内分泌功能

长期以来,骨骼肌被认为是一种效应器官,接受神经和体液的调节。近年大量实验研究资料发现骨骼肌也具有分泌活性物质的功能,能表达、合成和分泌多种生物信号分子,包括调节肽、细胞因子和生长因子等,也是一种重要的内分泌器官。骨骼肌分泌的活性物质以旁分泌和／或自分泌方式调节骨骼肌的生长、代谢和运动功能;甚至以血液循环内分泌的方式调节机体远隔器官组织的功能。骨骼肌生成和分泌的活性物质在运动系统疾病和某些全身性疾病的发病中具有重要的作用。本文将对骨骼肌分泌的主要活性物质及其生理和病理生理学意义进行综述。     

细胞因子网络调控与免疫性血小板减少性紫癜相关性研究

细胞因子是由免疫细胞和某些非免疫细胞经刺激而合成分泌的一类具有广泛生物学活性的小分子蛋白,它在机体正常和异常的生命活动过程中均具有重要而复杂的生物学作用,它们之间通过合成和分泌的相互调节.受体表达的相互调节、生物学效应的相互影响等组成一个复杂的细胞因子网络.免疫性血小板减少性紫癜(ITP)是一种以血小板减少和皮肤粘膜出血为特征的自身免疫性疾病,研究表明细胞因子水平的异常导致的细胞因子网络失衡在ITP发病中具有重要作用.细胞因子疗法已被用于自身免疫性疾病,随着细胞因子网络与ITP研究的不断深入和基因工程技术、细胞分子生物技术的日趋成熟,细胞因子疗法将成为治疗ITP的有效措施.     

一氧化氮和细胞因子之间的相互调节作用

一氧化氮（ＮＯ）作为一种信使参与炎症反应、信号转导、免疫调节及血管舒张等多种功能调节,在许多因素刺激下巨噬细胞产生ＮＯ恺 人知,而本文主要简述了淋巴细胞ＮＯ的产生,以及ＮＯ对淋巴细胞增殖的抑制作用及相关的信号转导通路;淋巴细胞产生的许多细胞因子可以影响自身及巨噬细胞ＮＯ的产生,而ＮＯ又反过来影响细胞因子的产生,不同免疫细胞所分泌的细胞因子效互调节影响Ｔｈ１细胞／Ｔｈ２细胞间的平衡状态,从而介导了自     

促性腺激素释放激素的免疫调节功能

随着对神经与免疫系统相互作用研究的深入,神经激素在免疫系统中的作用越来越多地被关注。由下丘脑合成的促性腺激素释放激素(gonadotropin-releasing hormone,Gn RH)及其受体均在免疫细胞中被发现,表明Gn RH在免疫系统内具有自分泌或旁分泌作用,对机体免疫反应、免疫细胞的活性与增殖、免疫介质释放和细胞功能具有免疫调节作用,对自身免疫疾病也有一定的影响。Gn RH可能是免疫系统调节的重要组成部分,在调节免疫介导的疾病中发挥作用,对于构建神经、免疫、内分泌三大系统互相调节网络起到了重要的作用。     

细胞因子和microRNA与结核分枝杆菌感染的研究进展

细胞因子是由免疫细胞和某些非免疫细胞经刺激而合成、分泌的一类具有广泛生物学活性的小分子蛋白质,其作为细胞间信号传递分子,主要参与调节免疫应答、免疫细胞分化发育、组织修复、介导炎症反应、刺激造血功能等。micro RNA(mi RNA)是存在于真核细胞内的一种非编码小RNA,可以调控基因转录后的表达,同时还可作为不同生理和病理状态的分子标记。许多研究表明,细胞因子相关基因的多态性与结核感染、肺结核发病易感性密切相关,而mi RNA在肺部疾病的正负调节功能与肺部疾病感染的发生、发展、转化与治疗有关。我们简要叙述了细胞因子、mi RNA与结核分枝杆菌感染三者之间的关联,以期有利于及时筛查潜伏结核感染和肺结核患者,降低结核感染率和发病率。     

细胞因子在脑缺血中的介导作用

脑缺血后内皮细胞及其它活性细胞可分泌多种细胞因子 ,而许多细胞因子又可反作用于内皮细胞 ,破坏血脑屏障的完整性 ,进而造成脑神经损害。本文综合阐述脑缺血损害病理过程中起主要作用的细胞因子。1　白介素 - 1 ( IL- 1 )　　IL- 1可由多种活性细胞合成分泌 ,胶质细胞和内皮细胞也可合成 ,它是一类具有广泛作用的多肽。人 IL- 1分子量为 1 5～ 1 7KD,活性形式有 IL-1α、 IL - 1β、 IL - 1 rα三种形式。 IL - 1β是血浆和组织液中的主要形式 ,也是脑组织中的主要形式。它不仅能够协同其它细胞因子促进 B、T细胞活化 ,而且能够诱…     

嘌呤P2受体的免疫调节功能

嘌呤P2受体(purinergic P2 receptors)是一类核酸及其衍生物受体,被激活后可调节免疫反应,如能够介导免疫细胞向炎症部位的迁移,影响免疫细胞的增殖、分化和凋亡以及影响其分泌的细胞因子和趋化因子来调节炎症。该文介绍了嘌呤P2受体的分类、在免疫细胞上的分布情况以及它们在调节免疫反应中的功能。     

白介素21及其对肿瘤的抑制作用

白介素21(interleukin-21, IL-21)是新近发现的具有多效免疫调节活性的细胞因子.遗传学和生化分析证实,IL-21是IL-2细胞因子家族的新成员.IL-21受体复合物包含γc-受体亚单位,活化后可引起JAK/STAT信号转导级联放大效应.IL-21由活化的CD4 T细胞合成,调节B细胞、T细胞、NK细胞和树突状细胞的增殖和分化.IL-21通过增强IgG抗体应答反应,抑制IgE合成而调节正常的体液免疫.IL-21也是重要的细胞免疫调节子,通过调节CD8 T细胞和NK细胞的活性清除鼠的肿瘤.     

Impact of substance P on cellular immunity

Much evidence suggests a cross-talking between nerve fibers and the immunity system. The immunomodulation by substance P includes cell activation and proliferation of human cells, with cytokine and chemokine generation and release. Substance P was first isolated by Leeman et al. as an undecapeptide with important neurotransmitter-neuromodulator effects. In addition, substance P was shown to induce and mediate inflammation, angiogenesis, infections, intestinal mucosal immunity and stress. Substance P is able to activate several immune cells, such as CD4+ and CD8+ T lymphocytes, mast cells, NK cells and macrophages. In recent studies we have shown that substance P can activate interleukin-8, a CXC chemokine, demonstrating its involvement in immune cell chemoattraction. We believe that substance P is important in understanding the pathophysiology of inflammation.     

Inhibition of microglial egress in excised ganglia by human interleukin 10: implications for its activity in invertebrates

We studied the effects of recombinant human interleukin-10 (IL-10) on invertebrate immunocytes and microglia. The present report demonstrates that the spontaneous activation of invertebrate immunocytes can be specifically inhibited by recombinant human IL-10. Induced immunocyte activation by fMLP can also be significantly diminished by IL-10. This inhibition becomes apparent over hours and causes ameboid cells to become round and nonmobile. Furthermore, Mytilus edulis pedal ganglia maintained in culture, over the course of 24 hours, emit microglia. IL-10 significantly reduces this microglial egress, an action that can be diminished by concomitant exposure of the excised ganglia to an antibody specific to IL-10 as well as IL-10. The anti-IL-10 alone is without effect. Active-ameboid microglia that egress become round and inactive following IL-10 exposure, an action prevented by anti-IL-10. Lastly, a substance immunoreactively similar to human IL-10 can be detected in pedal ganglia homogenates. Taken together, and since the immunocytes and microglia are responding to IL-10, it implies that an IL-10-like substance could be present in invertebrates. In conclusion, the study demonstrates that both invertebrate immunocytes and microglia respond to IL-10, suggesting an early evolution of this generally inhibitory cytokine.     

Immunoreactive substance P in the chicken gut: Distribution,development and possible functional significance

Summary The distribution and cellular localization of substance P in the chicken gut was studied by immunocytochemistry and immunochemistry. Substance P-containing nerve fibers are numerous in the gut wall. They occur in the smooth muscle layer as well as in the mucosa, where they are associated with blood vessels or surround the intestinal crypts. The fibers are particularly numerous in the myenteric and submucosal plexuses, where substance P-containing nerve-cell perikarya are also encountered. Substance P was found also in scattered endocrine cells of the small intestine, caeca and colon. Previously, bombesin-containing cells, which are numerous in the proventriculus, have been mistakenly identified as substance P cells due to crossreactivity of certain antisera against substance P. Immunochemistry revealed the highest concentration of substance P in the duodenum. The gel chromatographic behavior of chicken substance P differs slightly from that of synthetic bovine substance P, suggesting that chicken substance P differs structurally from mammalian substance P. Substance P-containing nerve fibers in the chicken gut develop slowly after hatching, apparently beginning in the duodenum; at approximately 20 weeks after hatching the distribution pattern is fully developed.A functional investigation was performed on the isolated chicken caecum to clarify the role of substance P in the contractile behavior of smooth muscle. Substance P contracted the caecum over a wide dose range; the contractile response was greater in 20 week-old chickens than in 4 and 10 week-old animals. Electrical field stimulation caused a relaxation of the caecum and a contraction upon cessation of stimulation. Neither of these responses, both of which are neurally mediated, were inhibited by adrenergic and cholinergic blockade. It is conceivable that the contractile response following electrical stimulation is caused by substance P released from nerve fibers in the smooth muscle.     

Inhibition of substance P activity prevents stress-induced bladder damage

Substance P is a neuropeptide involved in inflammation, immune regulation and stress response. Stress may induce bladder damage by stimulating inflammatory response such as mast cell activation. We here examined the role substance P during stress-induced mast cell degranulation and urothelial injury in rat bladder. Adult Sprague-Dawley rats (200-270 g) were either exposed to cold-immobilization stress or substance P (SP) intracerebroventricularly. Different doses of substance P receptor (NK1R) antagonist CP 99994 were administered peripherally or centrally before the stress exposure. From each group, samples of the bladder were examined with light and electron microscope. Stress- and SP-injected centrally, increased the number of both granulated and degranulated mast cells. Ultrastructurally, urothelial degeneration with vacuolization in the cytoplasm and dilated intercellular spaces were seen. Both central and peripheral injection of CP 99994 prevented stress-induced urothelial degeneration as well as stress-induced mast cell degranulation. In conclusion, centrally and peripherally released substance P is involved in stress-induced bladder damage. Inhibition of NK1R prevents stress-induced pathological changes of urinary bladder and NK1R antagonist can be considered for the treatment of inflammatory bladder diseases.     

Substance P Protects Against Desensitization of the Nicotinic Response in Isolated Adrenal Chromaffin Cells

Substance P, a peptide endogenous to the splanchnic nerve, is known to inhibit the acetylcholine-and nicotine-induced release of catecholamines from isolated adrenal chromaffin cells. In the present study the effect of substance P on desensitization of catecholamine release from these cells was examined. Substance P (10(-5) M) completely protected against desensitization of catecholamine release produced by acetylcholine at 37 degrees C or 23 degrees C and by nicotine at 23 degrees C; substance P also afforded appreciable protection against nicotine-induced desensitization at 37 degrees C. The peptide had no effect on K+-induced desensitization of catecholamine release. Like substance P, d-tubocurarine also prevented nicotinic desensitization. Substance P prevented both of two components of nicotinic desensitization, i.e. the Ca2+-dependent component and the Ca2+-independent, depletion-independent component of desensitization. Substance P had little effect on subsequent catecholamine uptake, indicating that substance P's protection against desensitization is a result of facilitation of catecholamine release rather than inhibition of catecholamine reuptake. Nicotine-induced catecholamine release and nicotinic desensitization of catecholamine release were Na+-independent, although substance P's inhibition of nicotine-induced catecholamine release was reduced by extracellular Na+. These in vitro studies suggest a similar role for substance P in vivo: substance P's protection against nicotinic desensitization may ensure a maintained output of adrenal catecholamines during stress, when the splanchnic nerve releases large amounts of acetylcholine.     

Acute effect of substance P in immunologic vasculitis in the rat colon

Substance P has been implicated as a neuronal mediator of inflammation in various inflammatory conditions. However, the exact role played by substance P in inflammatory bowel diseases or in experimental colonic vasculitis has not been clearly understood. In this study, we examined the effect of close superior mesenteric artery injection of substance P under prevailing inflammatory conditions induced by intravenous human albumin antialbumin immune complex followed by intracolonic perfusion of 2.5% formaldehyde in rats or intracolonic perfusion of 5% alcohol alone. The immune complex- and formaldehyde-treated rats showed severe microvascular changes such as microvascular plugging by red blood cells, endothelial breakage and extravasation of plasma proteins and red blood cells. The bolus injection of 10⁻⁸ M substance P reduced extravasation of Evans blue dye by 50% and the tissue wet to dry ratio by 20% in immune complex- and formaldehyde-perfused rats. Myeloperoxidase activity was not changed. Substance P also significantly inhibited (44%) the extravasation in alcohol-perfused rats. Pretreatment of immune complex- and formaldehyde-treated rats with substance P antagonist reversed the effect of substance P. These findings suggest that the most immediate effect of substance P may be vasodilation and clearing of vascular plugs induced by immune complex and formaldehyde. This effect of substance P differs from its chronic effect, which causes vasodilation and extravasation.     

Substance P-containing nerve fibres in large peripheral blood vessels of the rat

Substance P-immunoreactive nerve fibres were localized by the indirect immunohistochemical method in the adventitia and the adventitial-medial border of large peripheral arteries and veins of the rat. Arteries showed a richer substance P-containing innervation than veins. The superior mesenteric artery was densely innervated, whereas no substance P-containing fibres were found around the carotid artery. Substance P produced a vasoconstriction of the veins, but was basically without effect on arteries, although with the carotid artery a dose-dependent relaxation was observed. The absence of a correlation between the degree of innervation of the blood vessels and their responsiveness to exogenous substance P suggests that there nerves do not subserve a vasomotor function. The depletion of substance P immunoreactivity from nerves in arteries and veins by capsaicin suggest that substance P-containing vascular nerves are primarily sensory in nature.     

Yessotoxin affects fMLP-induced cell shape changes inMytilus galloprovincialis immunocytes

Using computer-assisted microscopic image analysis, we have found that algal yessotoxin (YTX) affects the immune response of Mytilus galloprovincialis. Indeed, YTX increases immunocyte cell motility through the involvement of both extracellular Ca2+ and cAMP, but not through protein kinase A, protein kinase C or phosphoinositide 3-kinase. Alone, however, the toxin does not induce any effect, as its action on cell motility is observed only after addition of the chemotactic substance N-formyl-Meth-Leu-Phe (fMLP). fMLP is known to induce cellular changes via both the phosphatidylinositol and cAMP pathways and, from this scenario, we can surmise that Ca2+ and cAMP concentrations rise sufficiently in fMLP-activated immunocytes to reveal YTX action. One possible explanation is that the toxin increases fMLP-mediated cell activation by intervening in L-type Ca2+-channel opening through a cAMP-dependent/PKA-independent pathway.     

Neural control in the immunocytotoxic destruction of muscles in Diptera

Following successful escape from the puparium (eclosion), sets of muscles in all three segments of dipteran flies degenerate. Whereas the head and abdominal muscles degenerate in response to hormonal triggers released before, and immediately after eclosion, the thoracic muscles require a specific neural trigger encountered following eclosion. Evidence is presented for the role of neural activity in the activation of immunocytes that destroy the thoracic muscles. Removal of the neural input by severing the nerve to any particular muscle results in survival of the muscle and inactivation of the immunocyte. The destruction process can be stopped at any time by severing the nerve and the muscle fibres that remain continue to show normal physiology and response to stimulation. Elcctrophysiological recordings of the response to lethal attack are presented together with ultrastructural evidence demonstrating the invasion of muscle fibres by processes of the immunocyte.