Histamine: Its novel role as an endogenous regulator of Con A – dependent T cell proliferation

Objective and design:The roles of histamine formed by the macrophage – T lymphocyte system were evaluated in the regulation of lymphocyte proliferation using mice lacking histamine receptors. Methods:Mice deficient in histamine type 1 (H1R), type 2 (H2R) or both receptors were employed to estimate possible intervention of the receptors in the histamine-dependent lymphocyte proliferation. Results:Histamine was produced de novo by spleen cells. Con A-dependent T cell proliferation decreased when histamine produced in the culture was degraded by the addition of histaminase. The H2R-deficient mice also showed a significant decrease in the Con A-dependent T cell proliferation, whereas it was not modulated in the H1R-deleted mice. Consistent with the reduction in T cell proliferation, there was a significant down-regulation of the production of IL-2, a T cell growth factor, in the H2R-deficient mice. Con A-dependent IL-2 synthesis was abrogated by the addition of histaminase. Conclusions:Con A-dependent T cell proliferation is (up)regulated by histamine produced de novo through the H2R, suggesting that histamine is a newly found regulator of T cell proliferation.Received 18 October 2003; returned for revision 17 December 2003; accepted by M. J. Parnham 6 February 2004     

Macrophage mannose receptor in chronic sinus disease

BACKGROUND: The role of infectious agents in the onset and maintenance of chronic sinus disease is still not fully understood. Macrophage mannose receptor (MMR), an innate pattern recognizing receptor, capable of phagocytosis of invaders and signal transduction for proinflammatory mechanisms, might be of importance in immune interactions in chronic sinus disease. OBJECTIVE: We examined the MMR in sinonasal airway mucosa to evaluate its possible role in chronic rhinosinusitis (CS) and nasal polyposis (NPs). METHODS: Surgical samples from patients with sinonasal disease were investigated with real-time RT-PCR for quantification of MMR mRNA expression, and the presence and location of MMR-positive cells was analysed by immunohistochemistry. RESULTS: Quantification of MMR mRNA showed a statistically significant higher expression in NPs compared to CS without NP and controls. Immunohistochemistry revealed expression of MMR in all tissue samples; however, in NP we found an enhanced positive cellular staining including cell aggregates. CONCLUSIONS: We could demonstrate for the first time that the expression of MMR is significantly upregulated in NP compared to patients with CS without NP or turbinate tissue of controls. Macrophages expressing MMR, accumulated in cell aggregates in NPs, play a possible key role in pathogen-macrophage interaction in NP disease.     

Endogene Natriuretische und Ouabain-ähnliche Faktoren

Summary The existence of an endogenous natriuretic hormone and ouabain-like factors (OLF) has been postulated for many years. This postulate was based on our original observation that a small M.W. fraction in the serum after acute expansion of the extracellular fluid volume (ECFV) not only exhibited natriuretic activity but also inhibited the Na-K-ATPase enzyme in vitro similar to ouabain. Since then, numerous studies confirmed the presence of OLFs in serum, urine, cerebrospinal fluid, and various organs including the heart and hypothalamus. Some of these OLFs are well-known endogenous compounds, such as free unsaturated fatty acids, which inhibit in vitro transmembranous sodium transport, Na-K-ATPase and³H-ouabain binding to its membrane receptor or crossreact with digoxin antibodies. Chemically yet undefined OLFs of potentially hypothalamic origin were detected in various models of experimental and clinical hypertension and are suggested to play a pathophysiological role especially in salt- and volume-dependent forms of hypertension. Our results show that OLFs isolated from the urine of salt-loaded healthy subjects strongly enhance basal and vasopressin-stimulated release of calcium in vascular smooth muscle cells and platelets similar to the effects we had observed with endothelin. This urine fraction also exhibits natriuretic activity which increases in parallel with sodium intake. Further chromatographic separation and amino acid analysis confirmed the peptidic nature (M.W.<1000) of the natriuretic factor(s). However, the two biological activities, namely natriuretic and ouabain-like activities, reside in distinct and chemically different compounds. In face of the previous discovery of the atrial natriuretic peptides (ANP) it is of special interest that very recent observations strongly suggest a natriuretic factor of non-cardiac origin to play an important role in the natriuresis that follows ECFV expansion. In addition, numerous experimental data point to an interaction between the ANP and OLF systems. They should stimulate once again the final identification of these yet unknown endogenous natriuretic and ouabain-like factors.

Die in dieser übersicht zitierten eigenen Untersuchungen wurden von der Deutschen Forschungsgemeinschaft, Bonn, dem Ministerium für Wissenschaft und Forschung des Landes Nordrhein-Westfalen (FA-2914, FA-8871, IVA6-402-046-87), Düsseldorf, und der Konrad-Adenauer-Stiftung, Bonn, unterstützt     

Clinical, biochemical and immunoelectron microscopical evidence of dual hormone production in a mammosomatotroph cell adenoma

This paper reports the occurrence of a rare, yet distinct pituitary adenoma which was surgically removed from a 42-year-old male with both clinical and biochemical evidence of acromegaly and mild hyperprolactinaemia. The monomorphic adenoma consisted of mature cells which were ultrastructurally indistinguishable from those of a prolactinoma. Electron immunocytochemistry, including a series of double-labelling techniques using selected colloidal gold particles as markers, indicated the presence of a pituitary adenoma in which the cells were capable of simultaneously producing growth hormone and prolactin and packaging them within the same secretory granule. This is thought to represent a mammosomatotroph cell adenoma.     

Frequent occurrence of in vivo clonal expansion of CD4− CD8− T cells bearing T cell receptor αβ chains in adult humans

We have previously reported 2 cases of healthy men showing in vivo monoclonal expansion of mature CD4^? CD8^? αβ T cells. In the present study, an additional 3 adults were found to exhibit such an expansion, among a total 464 adult donors studied. These 5 individuals were otherwise physiologically normal, with no history of severe illness and autoimmune disease at the time of examination. To investigate the mechanisms of the clonal expansion, further characterization of the clonal cells was attempted. No apparent preference for usage of the Tcell receptor β chain variable region was observed in the clonal T cells. These clonal T cells showed lectin-dependent or redirected antibody-dependent cell-mediated cytotoxicities, whereas they could not lyse autologous lymphoblastoid cell lines. Failure of Fas antigen expression was not observed for any of these clones. These results suggest that clonal expansion of CD4^? CD8^? αβ T cells frequently occurs in the periphery without any T cell abnormalities.     

Lack of functional estrogen receptor beta influences anxiety behavior and serotonin content in female mice

Estrogen has been linked to the modulation of anxiety in females. Here we report results of anxiety tests conducted in female estrogen receptor beta (ERbeta) knockout (ERbetaKO) and wild-type (WT) mice. Ovariectomized (OVX) mice treated with chronic estradiol (E2) replacement did not behave differently on the elevated plus-maze when compared with OVX mice that did not experience hormone replacement. However, a genotype difference was noted; WT females were more likely to explore the distal portion of the open arm of the maze than ERbetaKO littermates. In addition, ERbetaKO female mice had significantly lower serotonin (5-HT) content than WT littermates in several brain regions including: the bed nucleus of the stria terminalis, preoptic area, and hippocampus. A similar trend was noted in the dorsal raphe nucleus. Dopamine content was reduced within the caudate putamen in ERbetaKO mice as compared to brains from WT animals. Thus, in the absence of functional ERbeta, regardless of the presence or absence of circulating E2 in plasma, female mice exhibited enhanced anxiety and decreased concentrations of 5-HT or dopamine in several brain regions. We hypothesize that ERbeta is required during development to modulate the effects of estrogen on anxiety and catecholamine concentrations in female mouse brains.     

Graves病患者TRAb与抗TSHAb抗体关系的初步研究

根据自身免疫性甲状腺疾病发病机制的独特型－抗独特型免疫免疫学说，用兔抗人ＴＳＨＡｂ检测ＴＳＨ抗独特型抗体（ＴＳＨＡｂ２）。以正常人为对照，以其结合率＾－ｘ＋２ｓ为正常值上限，大于此值为阳性。６０例ＴＲＡｂ阳性病人，６５％病人ＴＳＨＡｂ２阳性，而４０例ＴＲＡｂ阳性病人中，只有５％病人ＴＳＨＡｂ２阳性。两组差异显著（Ｐ〈０．０５）。ＴＲＡｂ和ＴＳＨＡｂ２呈正相关（ｒ＝０．６４５，Ｐ〈０．０１）。同时用     

Egfl7 knockdown causes defects in the extension and junctional arrangements of endothelial cells during zebrafish vasculogenesis.

The endothelial cell (EC) -specific secreted protein EGFL7 is important for tubulogenesis in newly forming blood vessels. We studied its role in vascular tube formation by a quantitative ultrastructural analysis of Egfl7-knockdown zebrafish embryos. At 24 hours postfertilization, the endothelia of dorsal aorta (DA) and posterior cardinal vein (PCV) were correctly anchored to the hypochord and endoderm, respectively, but failed to expand into the vascular area. This resulted in vessels with reduced or split lumen and open sheets of ECs. Concomitantly, the organization of hematopoietic cells-identified by the presence of previously undescribed membrane tubules-between DA and PCV, and within the vessels, was severely disturbed. Strikingly, ectopic cell junctions occurred across the obstructed vessel lumen, on the luminal EC surfaces, which in control conditions never display junctions of any kind. These data suggest that Egfl7 provides ECs with a cue for their extension into the vascular area and in establishing EC cell polarity.