The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells

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脑啡肽与生长抑素在鸡视网膜无长突细胞共存的免疫组织化学研究

本文介绍用免疫组织化学的单标和双标技术研究脑啡肽(ENK)和生长抑素(SOM)在鸡视网膜无长突细胞的定位和共存。单标的实验结果表明,一些SOM免疫反应阳性无长突细胞的形态、胞体在内核层的位置及其突起在内网层的分支式样与某些ENK免疫反应阳性无长突细胞相似,虽然其突起在内网层的第3、4亚层形成的丛网不象ENK免疫反应阳性突起那样丛密,在内网层的第5亚层也未见SOM免疫阳性突起。双标的实验结果表明,一些无长突细胞显示ENK和SOM两种免疫阳性反应,而另一些无长突细胞分别只显示ENK或SOM阳性免疫反应。文中还对视网膜神经多肽间或与经典神经递质的共存进行了讨论。     

Partial destruction of Borrelia burgdorferi within ticks that engorged on OspE- or OspF-immunized mice.

We determined whether Borrelia burgdorferi outer surface proteins (Osps) E and F could elicit immune responses useful for a Lyme disease vaccine. Thirty days after challenge with B. burgdorferi, mice produced antibodies to OspE but not OspF, whereas antibodies to OspF were present in sera of mice obtained 90 days after infection. Examination of sera from patients with Lyme disease revealed antibodies to OspF in a small number (14%) of early-stage disease patients but in a majority (58%) of patients with late-stage disease, while antibodies to OspE were rarely detected in patients. Mice immunized with recombinant OspE or OspF produced high titers of antibodies to OspE or OspF, respectively. OspF-immunized mice were partially protected from both intradermal syringe challenge and tick-mediated transmission of B. burgdorferi while vaccination with OspE did not confer immunity. B. burgdorferi organisms were, however, substantially destroyed within ticks that engorged on either OspE- (75% reduction in the number of spirochetes within the ticks, compared with controls) or OspF (90% reduction in the number of spirochetes within the ticks)-immunized mice.     

An inactivated temperature-sensitive mycoplasma gallisepticum mutant for protection against airsacculitis

A formalinised temperature-sensitive (TS) mutant of Mycoplasma gallisepticum (MG) emulsified in complete Freund's adjuvant was capable of protecting chickens against airsacculitis after intra-air sac challenge with the virulent S6 strain at a statistically significant level. Formalinised TS MG vaccine without the addition of adjuvant yielded inconsistent results, and the outcome may have been dependent upon the dosage used.     

Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains

Systemic lupus erythematosus (SLE) is an autoimmune disorder of a largely unknown etiology. Anti-double-stranded (ds) DNA antibodies are a classic hallmark of the disease, although the mechanism underlying their induction remains unclear. We demonstrate here that, in both lupus-prone and normal mouse strains, strong anti-dsDNA antibody responses can be induced by dendritic cells (DC) that have ingested syngeneic necrotic (DC/nec), but not apoptotic (DC/apo), cells. Clinical manifestations of lupus were evident, however, only in susceptible mouse strains, which correlate with the ability of DC/nec to release IFN-gamma and to induce the pathogenic IgG2a anti-dsDNA antibodies. Injection of DC/nec not only accelerated disease progression in the MRL/MpJ-lpr/lpr lupus-prone mice but also induced a lupus-like disease in the MRL/MpJ-+/+ wild-type control strain. Immune complex deposition was readily detectable in the kidneys, and the mice developed proteinuria. Strikingly, female MRL/MpJ-+/+ mice that had received DC/nec, but not DC/apo, developed a 'butterfly' facial lesion resembling a cardinal feature of human SLE. Our study therefore demonstrates that DC/nec inducing a Th1 type of responses, which are otherwise tightly regulated in a normal immune system, may play a pivotal role in SLE pathogenesis.     

Role of caspases in dexamethasone-induced apoptosis and activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase in human eosinophils

Eosinophils are the principal effector cells for the pathogenesis of allergic inflammation. Glucocorticoids such as dexamethasone have long been used therapeutically for eosinophilia in allergic inflammation by inducing eosinophil apoptosis, but little is known about the intracellular mechanisms mediating dexamethasone-induced apoptosis. In the present study, we investigated the effect of dexamethasone on three mitogen-activated protein kinases (MAPK) involved in the intracellular signalling pathway: c-Jun NH2-terminal kinase (JNK), p38 MAPK and extracellular signal-regulated kinase (ERK). We found that dexamethasone could activate JNK and p38 MAPK in a time-dependent manner but not ERK. Further, SB 203580, a specific p38 MAPK inhibitor, was additive with dexamethasone in inducing eosinophil apoptosis, while JNK1/2 antisense phosphorothioate oligodeoxynucleotides did not show any significant effect. These suggest that dexamethasone-induced JNK1/2 and p38 MAPK activation are not crucial to the induction of apoptosis. Pretreatment of eosinophils with benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD.FMK), a broad-spectrum caspase inhibitor, could inhibit dexamethasone-induced apoptosis in eosinophils dose-dependently. Moreover, Z-VAD.FMK partially inhibited dexamethasone-activated JNK and p38 MAPK activities. However, dexamethasone treatment did not activate specific caspase-3, -8 activity in eosinophils compared with spontaneous apoptosis. We therefore conclude that dexamethasone-induced apoptosis and activation of JNK and p38 MAPK activity in eosinophils are regulated by caspases but not through the common apoptosis-related caspase-3, -8 as in other cell types. Elucidation of the important role of caspases in eosinophil apoptosis may facilitate the development of more specific and effective treatment for allergic inflammation.     

Systemic oxidative and antioxidative status in Chinese patients with asthma

BACKGROUND: Patients with asthma generate an increased amount of reactive oxygen species from peripheral blood cells. Reactive oxygen species produce many of the pathophysiologic changes associated with asthma and may contribute to its pathogenesis. OBJECTIVE: We investigated changes in antioxidant enzyme activities and oxidized glutathione (glutathione disulfide; GSSG) levels in erythrocytes from a group of healthy control Chinese subjects (n=135) and patients with asthma (n=106). METHODS: Baseline pulmonary function was measured for all subjects. Antioxidant status was evaluated by measuring erythrocyte superoxide dismutase, catalase, and glutathione peroxidase activities. Oxidative stress was also measured in terms of GSSG in erythrocytes with a kinetic microassay. RESULTS: Patients with asthma had significantly increased erythrocyte superoxide dismutase and catalase activities compared with controls (61.10 +/- 1.30 U/g hemoglobin [Hb] vs 55.51 +/- 1.82 U/g Hb [P=.018] and 0.0637 +/- 0.0021 U/g Hb vs 0.0257 +/- 0.0120 U/g Hb [P <.001] for the asthma and control groups, respectively). Conversely, erythrocyte glutathione peroxidase activity decreased (44.21 +/- 1.33 mU/g Hb vs 50.07 +/- 1.39 mU/g Hb for the asthma and control groups, respectively; P=.003). Patients with asthma also had significantly higher GSSG levels in erythrocyte hemolysates compared with controls (167.40 +/- 2.93 micromol/L vs 44.98 +/- 0.44 micromol/L for the asthma and control groups, respectively; P <.001), indicating increased oxidative stress. CONCLUSIONS: Asthma is accompanied by an alteration in systemic antioxidant status due to possible oxidative stress in this disease.     

Cardiac Myxoma: Histochemical and Ultrastructural Localization of Glycosaminoglycans and Proteoglycans

A recurrent cardiac myxoma is examined histochemical ly at the ultrastructural level. By routine electron microscopy the stellate “myxoma” cell exhibits features suggestive of a secretory function in synthesis of its myxoid stroma. Spicer's high iron diamine (HID), which stains specifically for sulfated glycoconjugates, is utilized for intracellular localization of glycosaminoglycans. HID-positive reactive sites are localized within the Golgi-derived vacuoles and secretory granules of the myxoma cells. No staining is obtained with other cytoplasmic organelles except rare secondary lyso-somes. Although colloidal iron is less specific, both intracellular and extracellular positive reactive sites are observed. With ruthenium red staining the proteoglycans in the extracellular stroma can be visualized as numerous positively stained, polygonal 250-500 A matrix granules with faint filamentous projections. Positive intracellular ruthenium red-stained granules are also observed within the Golgi-derived vacuoles. The alcianophilia of the myxoid stroma with Alcian blue is almost completely abolished by prior treatment with bovine testicular hyaluronidase but is unaffected by leech hyaluronidase, indicating chondroitin sulfates A and/or C, not hyaluronic acid, as the major biochemical constituents of the stroma and the observed extracellular matrix granules. The above findings provide cytochemical evidence of intracellular synthesis of sulfated glycosaminoglycans and proteoglycans of the myxoma cell and its active participation in production of its stroma.