Mast cells and inflammation

Mast cells are well known for their role in allergic and anaphylactic reactions, as well as their involvement in acquired and innate immunity. Increasing evidence now implicates mast cells in inflammatory diseases where they are activated by non-allergic triggers, such as neuropeptides and cytokines, often exerting synergistic effects as in the case of IL-33 and neurotensin. Mast cells can also release pro-inflammatory mediators selectively without degranulation. In particular, IL-1 induces selective release of IL-6, while corticotropin-releasing hormone secreted under stress induces the release of vascular endothelial growth factor. Many inflammatory diseases involve mast cells in cross-talk with T cells, such as atopic dermatitis, psoriasis and multiple sclerosis, which all worsen by stress. How mast cell differential responses are regulated is still unresolved. Preliminary evidence suggests that mitochondrial function and dynamics control mast cell degranulation, but not selective release. Recent findings also indicate that mast cells have immunomodulatory properties. Understanding selective release of mediators could explain how mast cells participate in numerous diverse biologic processes, and how they exert both immunostimulatory and immunosuppressive actions. Unraveling selective mast cell secretion could also help develop unique mast cell inhibitors with novel therapeutic applications. This article is part of a Special Issue entitled: Mast cells in inflammation.     

老年人动态心电图心律失常特点及对阵发性 房颤的诊断

目的:分析65岁以上老年人十二导联动态心电图(12-Holter)心律失常的特点及其对阵发性房颤的诊断价值。方法:①采用回顾性分析的方法,随机选择500例65岁以上老年人的动态心电图进行心律失常情况的统计分析,并同时选择500例小于65岁的心电图作为对照;②另选择500例65岁以上老年人的十二导联普通心电图(ECG)作为对照,对比分析12-Holter与ECG两种方法对老年人阵发性房颤的检出率。结果:①65岁以上老年人动态心电图各种心律失常、ST-T改变的发生率高。而在各类心律失常中房性早搏、室性期前收缩、房性心动过速、房颤发生率较高。②动态心电图对于阵发性房颤的检出率显著高于普通十二导联心电图。结论:①老年人动态心电图检查结果异常率高;②与普通心电图比较,动态心电图诊断老年人阵发性房颤有较高的价值。     

血小板活化因子对大鼠卵巢颗粒细胞垂体腺苷酸环化酶激活肽mRNA表达的影响及调节机制

目的：探讨血小板活化因子（PAF）对大鼠卵巢颗粒细胞垂体腺苷酸环化酶激活肽（PACAP）mRNA表达的影响及其可能调节机制,旨在寻找PAF在卵巢中的作用靶点。方法：原代培养卵巢颗粒细胞,用放射免疫分析（RIA）及逆转录．聚合酶链反应（RT-PCR）方法检测颗粒细胞雌二醇分泌情况及其PACAP mRNA表达变化．结果：PAF对PACAP mRNA表达无明显影响,但与hCG共同作用可促进PACAP mRNA的表达：Forkolin可使PACAP mRNA表达升高。结论：PAF可通过对hCG的允许作用间接促进大鼠卵巢颗粒细胞PACAP mRNA表达,hCG的促进作用可能是通过cAMP—PKA途径介导的。     

Stress molecules in sepsis and systemic inflammatory response syndrome

During sepsis, microbial derived products ("pathogen-associated molecular patterns", PAMPs) are recognized as exogenous danger signals by specific sensors of the host ("pattern recognitions receptors", PRRs). This interaction leads to the release of numerous stress proteins that are a prerequisite to fight infection, though their overzealous production can contribute to tissue damage, organ dysfunction and eventually death. In critically ill patients, translocation of PAMPs can occur from the gut, and injured tissues and cells release endogenous danger signals called "alarmins" (e.g. High mobility group box-1); that share some properties with PAMPs. Thus, numerous similarities occur during infectious and non-infectious systemic inflammation.     

Conversion of 1-alkyl-2-acetyl-sn-glycerols to platelet activating factor and related phospholipids by rabbit platelets

Bleomycin is an anti-tumor agent whose cytotoxicity is related to the introduction of both single-stranded and double-stranded breaks in cellular DNA. In an assay using isolated nuclei, low levels of ethidium bromide substantially increased bleomycin induced release of nuclear chromatin. Treatment of mouse L1210 leukemia cells in vitro with low levels of ethidium bromide followed 1 hr later by bleomycin produced a synergistic effect that was 8 fold greater than that expected from the additive cytotoxicity of each drug alone. Interestingly, when the order of drug addition was reversed the drug synergism was much reduced (2 fold). The combination of DNA unwinding and strand scission agents may represent a novel and rational approach to the chemotherapy of cancer.     

Molecular heterogeneity of platelet-activating factor produced by stimulated human polymorphonuclear leukocytes

The molecular heterogeneity of platelet-activating factor (PAF) produced by stimulated human neutrophilic polymorphonuclear leukocytes (PMN) was assessed by both normal and reverse phase high performance liquid chromatography (HPLC). As detected by rabbit platelet stimulation, at least 5 PAF molecules were separated by HPLC. Fast atom bombardment (FAB) mass spectrometry revealed one of these PAFs was acetyl glyceryl ether phosphorylcholine (AGEPC) with a C_16:0 alkyl chain in the $\text{sn}$-1 position. Although the structures of the remaining PAFs are unknown, two of the peaks of PAF activity had the same retention times on reverse phase HPLC as the C₁₅- and C₁₈-saturated alkyl chain AGEPC homologues. These studies indicate that the human PMN produces multiple molecular species of PAF.     

Preventive effect of several drugs againstPseudomonas aeruginosa infection and the toxicity of combined tumor necrosis factor with lipopolysaccharide: Relationship between lethality and the arachidonic cascade

The participation of tumor necrosis factor (TNF) and lipopolysaccharide (LPS) inPseudomonas aeruginosa (Pa) infection was examined. The lethal challenge of Pa or TNF and LPS injection could be prevented by pretreatment with anti-TNF antibody, polymyxin B, ONO 1078, or Shosaiko-to. The combined effects of TNF and LPS may be deeply related to the lethality of Pa infection. The activities of leukotriene(LT) C₄/D₄/E₄ or platelet activating factor (PAF) were also related to the lethality of Pa infection, probably due to the subsequently produced TNF which acts in combination with LPS. Activating the host defence mechanism with biological response modifiers like Chinese medicines was effective against Pa infection. One mechanism could involve an activity as an LT inhibitor or PAF antagonist. Following the administration of TNF and/or LPS, the serum levels of arachidonic cascade products underwent various changes. With a combination of TNF and LPS, there was a synergistic increment of prostaglandins, thromboxane, and LT. Following pretreatment with Shosaiko-to, suppression of LTs was dominant even with the combination of TNF and LPS, which might be related to the lethality of the infection or combined TNF with LPS.     

Lipid metabolism of myocardial endothelial cells

The vascular endothelium can be regarded as a widely distributed organ, interposed between the intravascular and extravascular spaces, with a pluripotent function in the regulation of capillary diameter, vascular homeostasis, lipoprotein metabolism and the vascular response to injury. In the basal physiological state these processes provide a non-thrombotic, non-inflammatory vascular lining preventing uncontrolled inflammation and coagulation. Endothelial cells respond to potential harmful conditions (mechanical stress, anoxia, ischemia and oxidative stress) and a variety of hormones and vasoactive mediators by inducing coagulation and production of inflammatory mediators through the production of bioactive lipids. Although the number of studies in isolated myocardial endothelial cells is limited, from the presumed metabolic analogy with endothelial cells isolated (and cultured) from other organs, one may conclude that the bioactive lipids include oxygenated arachidonate metabolites (eicosanoids) and the platelet activating factor (1--O-alkyl-2-acetyl-sn-glycerol-3-phosphocholine; PAF). All aspects of lipid metabolism, related to the production of eicosanoids and PAF, are present within myocardial endothelial cells. There is uptake and incorporation of fatty acids by endothelial cells and liberation from endogenous triacylglycerol and (membrane) phospholipid stores by (phospho)lipases. Endothelial cells oxidize fatty acids in a carnitine-dependent, mitochondrial, pathway. Endothelial cells actively interact with high density lipoprotein (HDL) and low density lipoprotein (LDL) leading to uptake of cholesterol(esters) that undergo intracellular hydrolysis, and re-esterification to phosphoand neutral lipids, and leaving the LDL-particle modified in a way that makes them bind to the scavenger receptor on macrophages. Extravascular triacylglycerols in lipoproteins (very low density lipoprotein (VLDL), chylomicrons) are handled by endothelial cell lipoprotein lipase, providing substrate fatty acids for the underlying muscle tissue. Eicosanoid production from (membrane)phospholipids and PAF synthesis from alkylphospholipids are tightly coupled and interrelated to the flow of arachidonic acid between cellular lipid pools. (Mol Cell Biochem116: 171–179, 1992)     

The unfolding story of two lissencephaly genes and brain development

Formation of our highly structured human brain involves a cascade of events, including differentiation, fate determination, and migration of neural precursors. In humans, unlike many other organisms, the cerebral cortex is the largest component of the brain. As in other mammals, the human cerebral cortex is located on the surface of the telencephalon and generally consists of six layers that are formed in an orderly fashion. During neuronal development, newly born neurons, moving in a radial direction, must migrate through previously formed layers to reach their proper cortical position. This is one of several neuronal migration routes that takes place in the developing brain; other modes of migration are tangential. Abnormal neuronal migration may in turn result in abnormal development of the cortical layers and deleterious consequences, such as Lissencephaly. Lissencephaly, a severe brain malformation, can be caused by mutations in one of two known genes:LIS1 anddoublecortin (DCX). Recent in vitro and in vivo studies, report on possible functions for these gene products.     

竹叶椒抑制血小板活化因子（PAF）的活性成分

自芸香科花椒属植物竹叶椒（Zanthoxglum planispinum Sieb.et Zucc）根和茎的石油醚及二氯甲烷提取物中分离得到5个化合物（I～V）,经物理常数测定,光谱（UV,IR,HNMR,MS）分析分别鉴定,Ⅰ为β-香木脂醇,Ⅱ为β-谷甾醇,Ⅲ为L-细辛脂素,Ⅳ为L-竹叶椒脂素,V为花椒明碱。其中Ⅲ,IV,V具有抑制PAF聚集的活性,以Ⅳ活性最强,Ⅲ次之,V较弱。花椒明碱首次从该植物中分离得到。