5—羟色胺免疫调节作用研究进展

５－羟色胺（５－ＨＴ）在体内广泛分布并具有多种生物学活性。近年许多研究表明５－ＨＴ可以通过受体作用于Ｔ、Ｂ淋巴细胞、ＮＫ细胞和ＭХ;对ＤＴＨ、ＮＫＣＣ、淋巴细胞增殖活性和ＭХ吞噬活性均有调节作用,是神经内分泌免疫调节网络的重要成分。     

间充质干细胞的免疫调节作用研究进展

间充质干细胞(mesenchymal stem cell,MSCs)属于成体干细胞,其具有广阔的临床应用前景.近年来人们发现MSCs有较强的免疫调节能力,并成功的将其用于治疗移植物抗宿主病(graft versus host disease,GVHD).据此推测MSCs对于其它慢性炎症性或者免疫相关性疾病可能同样具有治疗作用.本文将从MSCs对各类免疫细胞的作用、可能的机制、相关的动物实验以及临床研究等方面对MSCs的免疫调节作用研究进展作一综述.     

肠粘膜上皮细胞在粘膜免疫调节中的作用

肠粘膜上皮细胞是调节宿主粘膜表面自然免疫与获得性免疫的主要细胞。近年来的研究证实,IECS可以发挥多种免疫调节功能,如抗原提呈功能,分泌细胞因子,表达粘附分子等,本文重点介绍其分泌的几种细胞因子包括IL－1 Ra,IL-7,IL-8,TGF-β,SCF等与其免疫学功能的关系。     

家蝇蛹凝集素的免疫调节作用

本实验研究了从家蝇蛹体内分离的一种凝集素,研究了其免疫调节的性质。首先将收集的家蝇蛹在缓冲液中研磨,得到粗提物,经过亲和吸附、竞争洗脱等步骤得到了纯品。电泳结果表明家蝇蛹凝集素分子量大约为55kD。通过检测巨噬细胞分泌的细胞因子IL-6、IL-12等实验,证明了家蝇蛹凝集素浓度在5μg/mL时对与巨噬细胞分泌IL-6有显著增强作用,家蝇蛹凝集素的浓度在10μg/mL时对巨噬细胞分泌IL-12有显著效果。通过小鼠脾淋巴细胞增殖试验结果可知家蝇蛹凝集素对于混合淋巴细胞增殖有促进作用。以上试验结果说明家蝇蛹凝集素免疫调节作用,为天然免疫增强剂的开发提供了一定的参考依据。     

β—内啡肽的免疫调节作用

越来越多的证据表明,神经系统与免疫系统间存在着双向作用,而内源性阿片肽在这一双向关系中起重要的介质作用,本文就β－内啡肽（β－ＥＰ）在免疫系统中的作用作一综述。     

P物质的分子神经生物学研究进展

Ｐ物质的分子神经生物学得到了较广泛的研究,其中包括Ｐ物质的生物合成与调节、活性构象、释放与灭活、对膜通道的影响以及Ｐ物质受体的分子生物学等。另外,还涉及到了Ｐ物质Ｎ端片段的功能及结全位点。这些工作为从分子水平上进上步阐明Ｐ物质在神经系统中纷繁而重要的生理功能奠定了基础。     

P物质在应激活化小鼠皮肤肥大细胞中的作用

目的探讨P物质(substance P,SP)在应激活化小鼠皮肤肥大细胞中的作用。方法应用Communication box系统使小鼠分别负荷足电击和心理性应激,采用甲苯胺蓝(toluidine blue)染色法、免疫组化ABC技术分别检测皮肤肥大细胞数及SP阳性神经纤维数,以ELISA法检测皮肤中SP含量,以I125放免法测定血浆类固醇浓度。结果躯体性应激和心理性应激均可使血浆类固醇升高,躯体性应激负荷鼠的血浆类固醇激素在第3d达高峰,而后逐渐下降;而心理性应激负荷鼠的血浆类固醇激素在第5d达高峰后逐渐下降。腹腔注射WIN51078可明显降低两种应激负荷所致的血浆类固醇浓度,且对足电击的抑制效果优于心理性应激。足电击和心理性应激均可有意义增强皮肤肥大细胞的活化,增加SP阳性神经纤维数。足电击可使皮肤SP含量呈现有意义的减少,而心理性应激则皮肤SP含量增加,这些变化可因非肽性NK1速激肽受体拮抗剂WIN51078的腹腔注射而抑制。结论SP参与了应激导致的肥大细胞活化机制,同时显示了速激肽受体拮抗剂可能会抑制应激导致的皮肤症状的恶化。     

Cardiovascular interactions between methionine-enkephalin and substance P in the conscious dog

Interactions between the undecapeptide Substance P (SP) and the pentapeptide methionine-enkephalin (Met5-ENK) have been described in isolated organ systems and in baroreceptor reflex mechanisms. Previous studies in our laboratory have demonstrated that systemically injected Met5-ENK simultaneously increases mean systemic arterial pressure (MAP) and heart rate (HR) in the conscious, chronically instrumented dog. We have now evaluated cardiovascular interactions between SP and Met5-ENK. In this model, SP injected intravenously produces a rapid and transient decrease in MAP and increase in HR over the dose range from 1.0 to 10.0 ng/kg. SP does not appear to appreciably alter subsequent responses to Met5-ENK. At SP doses of 1.0 ng/kg, the peak hemodynamic response to SP and Met5-ENK (35 micrograms/kg) given together appears to represent a simple summation effect of both drugs on HR and MAP. However, at higher SP doses (5.0 ng/kg), the SP response predominates and is little altered by the presence of Met5-ENK. Thus, Met5-ENK does appear capable of modulating the hemodynamic responses to SP over certain dose ranges.     

Direct antimicrobial properties of substance P

The structural similarity between substance P (SP, Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH(2)) and Arg/Pro rich bactericidal peptides suggests a possible direct effect of SP on invasive microbes. We now present evidence that substance P possesses direct antimicrobial activity, highest against S. aureus. A substance P antagonist also possesses such activity but while less potent than substance P agonist S. aureus, is more potent than substance P against C. albicans. Our data also show that the endogenous peptides bradykinin and neurotensin, that also play role in modulation of the host-defense system in situ, have antimicrobial properties but are less potent than substance P.     

Active Uptake of Substance P Carboxy-Terminal Heptapeptide (5–11) into Rat Brain and Rabbit Spinal Cord Slices

We previously reported that nerve terminals and glial cells lack an active uptake system capable of terminating transmitter action of substance P (SP). In the present study, we demonstrated the existence of an active uptake system for SP carboxy-terminal heptapeptide, (5-11)SP. When the slices from either rat brain or rabbit spinal cord were incubated with [3H](5-11)SP, the uptake of (5-11)SP into slices was observed. The uptake system has the properties of an active transport mechanism: it is dependent on temperature and sensitive to hypoosmotic treatment and is inhibited by ouabain and dinitrophenol (DNP). In the brain, (5-11)SP was accumulated by means of a high-affinity and a low-affinity uptake system. The Km and the Vmax values for the high-affinity system were 4.20 x 10(-8) M and 7.59 fmol/10 mg wet weight/min, respectively, whereas these values for the low-affinity system were 1.00 x 10(-6) M and 100 fmol/10 mg wet weight/min, respectively. In the spinal cord, there was only one uptake system, with a Km value of 2.16 x 10(-7) M and Vmax value of 26.2 fmol/10 mg wet weight/min. These results suggest that when SP is released from nerve terminals, it is hydrolysed into (5-11)SP before or after acting as a neurotransmitter, which is in turn accumulated into nerve terminals. Therefore, the uptake system may represent a possible mechanism for the inactivation of SP.     

Measurement of Substance P Metabolites in Rat CNS

A procedure based on ion-exchange chromatography for chemical separation and radioimmunoassays for quantitation of substance P (SP), the SP(1-7), and C-terminal fragments, respectively, has been developed. The procedure allows the determination of these fragments in the presence of large (i.e., 50- to 100-fold) excess of parent compound. The chemical identity of isolated SP and fragments was studied with preparative electrophoresis on dilute agarose gel and with HPLC. The activity identified as SP(1-7) comigrated with the authentic standard whereas practically all activity isolated as C-terminal fragments comigrated with SP(5-11). The levels of C-terminal fragments in rat brain areas rich in SP and in spinal cord were 1-2% of those of parent compound. The levels of SP(1-7) were always higher, in the spinal cord markedly higher (three to five times). Postmortem storage of samples from brain and spinal cord indicated that SP(1-7) levels fell more rapidly than those of SP or C-terminal fragments.     

Demonstration and Distribution of Kassinin-Like Material (Substance K) in the Rat Central Nervous System

Antiserum was raised against kassinin in rabbits. Cross-reactivity with other tachykinins was determined; these included substance K (100%) and substance P (0.1%). Peptides extracted from rat brain and synthetic tachykinins were chromatographed by reverse-phase HPLC. The major peak of kassinin-like material eluted at a time different from that of synthetic kassinin, eledoisin, physalaemin, neurokinin beta, and substance P but coeluted with substance K. Measurement of kassinin-like material in macrodissected and microdissected brain regions indicated that the distribution of kassinin-like material was similar to that of substance P.     

The role of oxygen radicals in immune complex injury

In this review we will summarize our current understanding of the mediation of immune complex induced tissue injury. Comparisons will be made between the mediation of IgG versus IgA immune complex injury with emphasis on the role that reactive oxygen products derived from leukocytic phagocytic cells play in the initiation of the tissue injury.     

From cells to signaling cascades: manipulation of innate immunity by Toxoplasma gondii

The intracellular opportunistic protozoan Toxoplasma gondii is a potent stimulus for cell-mediated immunity, and IL-12-dependent IFN-gamma induction is vital in resistance to the parasite. Dendritic cells, neutrophils and macrophages are important sources of IL-12 during infection. T. gondii possesses two mechanisms for triggering IL-12. One is dependent upon the common adaptor protein MyD88, and is likely to involve Toll-like receptors. The other is a more unusual pathway that involves triggering through CCR5 by a parasite cyclophilin molecule. Countering these potent pro-inflammatory activities, T. gondii has several mechanisms to down-regulate immunity. Intracellular infection causes a blockade in the NFkappaB macrophage signaling pathway, correlating with reduced capacity for IL-12 and TNF-alpha production. The parasite also prevents STAT1 activity, resulting in decreased levels of IFN-gamma-stimulated MHC surface antigen expression. Furthermore, infection also induces resistance to apoptosis through inhibition of caspase activity. Extracellular pathways of suppression involve soluble mediators such as IL-10 and lipoxins that have potent IL-12 down-regulatory effects. The balance of pro-inflammatory and anti-inflammatory signaling which T. gondii engages is likely dictated by requirements for a stable host-parasite interaction. First, there is a need for Toxoplasma to induce an immune response robust enough to allow host survival and establish long-term chronic infection. Second, the parasite must avoid immune-elimination and induction of pro-inflammatory pathology that can cause lethality if unchecked. The widespread distribution of T. gondii and the normally innocuous nature of infection indicate the skill with which the parasite achieves the two seemingly contrary goals.     

Identification of substance P metabolites using a combination of reversed-phase high-performance liquid chromatography and capillary electrophoresis

Gradient elution reversed-phase high-performance liquid chromatographic and capillary electrophoretic separations were optimised to separate substance P (SP) and twelve of its fragments. The methods were applied to a study of the in vivo metabolism of substance P in the rat after intrastriatal injection of the peptide (10 nmol). SP and significant amounts of its N-terminal fragments, SP(1-7) and SP(1-4), were detected but no major C-terminal fragments could be identified. At the concentration studied, the metabolism of SP was shown to follow zero order elimination kinetics with a rate of decay of 0.2 nmol/min. As we have shown that SP(1–4) and SP(1–7) can be produced in vivo in the striatum in relatively large amounts, it is conceivable that these fragments contribute to the overall pharmacological pattern of activity of the parent peptide.