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101.
Platelet factor 4 (PF-4)-induced neutrophil adhesion is controlled by src-kinases, whereas PF-4-mediated exocytosis requires the additional activation of p38 MAP kinase and phosphatidylinositol 3-kinase
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Among the various chemokines that are functionally active on neutrophils, platelet factor 4 (PF-4; CXCL4) appears to have a specialized role. Lacking typical chemokine activities, PF-4 stimulates neutrophils to undergo firm adhesion to endothelial cells and, in the presence of an appropriate costimulus like tumor necrosis factor (TNF), PF-4 induces exocytosis of secondary granule contents. Analyzing the individual contribution of PF-4 and its costimuli in the control of these functions at the signaling level, we demonstrate that TNF-induced activation of p38 mitogen-activated protein (MAP) kinase (but not extracellular regulated kinase [Erk] kinases) acts as general and essential costimulatory signal in PF-4-dependent neutrophil exocytosis. This was shown by the use of a specific inhibitor (SB203580), by biologic (lipopolysaccharide, N-formyl-methionyl-leucyl-phenylalanine) and pharmacologic (anisomycin) activators of p38 MAP kinase, and by phosphorylation studies. Furthermore, TNF-mediated activation of phosphatidylinositol 3-kinase (PI 3-kinase) represents an additional essential signaling component in this process as demonstrated by studies with its inhibitor wortmannin as well as by analysis of the phosphorylation of AKT kinase. PF-4, however, directly activates src-kinases and PF-4-induced adherence as well as PF-4/TNF-mediated exocytosis was inhibited by an src-kinase inhibitor PP1. Taken together, neutrophil exocytosis and adherence are regulated on p38 MAP kinase, PI 3-kinase, and src-kinase activation. 相似文献
102.
Conditional mineralocorticoid receptor expression in the heart leads to life-threatening arrhythmias
103.
Avery DT Ma CS Bryant VL Santner-Nanan B Nanan R Wong M Fulcher DA Cook MC Tangye SG 《Blood》2008,112(5):1784-1793
The production of immunoglobulin E (IgE) is tightly regulated. This is evidenced by the fact that it comprises less than 0.0001% of serum Ig, and aberrant production causes atopic conditions, including allergy, rhinitis, and anaphylaxis. Interleukin-4 (IL-4) is a well-characterized inducer of IgE by human and murine B cells, whereas interferon-gamma can antagonize this effect. IL-21 has also been recognized for its ability to suppress IL-4-induced IgE production by murine B cells. Here, we identified IL-21 as an inducer of IgE production by CD40L-stimulated human naive B cells. Furthermore, there was a striking synergy between IL-4 and IL-21 on inducing IgE secretion by CD40L-stimulated human B cells, such that the levels detected under these conditions exceeded those induced by IL-4 or IL-21 alone by more than 10-fold. IL-21 induced activation of STAT3 and analysis of B cells from patients with loss-of-function STAT3 mutations revealed that the ability of IL-21 to induce IgE secretion, and augment that driven by IL-4, was STAT3-dependent. These findings highlight a fundamental difference between the regulation of IgE production by human and murine B cells and have implications for the dysregulated production of IgE in conditions characterized by extremely high levels of serum IgE. 相似文献
104.
MIP-1alpha, MIP-1beta, RANTES, and ATAC/lymphotactin function together with IFN-gamma as type 1 cytokines 总被引:3,自引:0,他引:3
Dorner BG Scheffold A Rolph MS Huser MB Kaufmann SH Radbruch A Flesch IE Kroczek RA 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(9):6181-6186
We analyzed for the first time the expression of chemokines in subpopulations of the murine immune system at the single-cell level. We demonstrate in vitro and in a model of murine listeriosis that macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, regulated on activation normal T cell expressed and secreted (RANTES), and activation-induced, T cell-derived, and chemokine-related cytokine (ATAC)/lymphotactin are cosecreted to a high degree with IFN-gamma by activated individual natural killer (NK), CD8(+) T, and CD4(+) T helper 1 (Th1) cells. Functionally, ATAC and the CC chemokines cooperate with IFN-gamma in the up-regulation of CD40, IL-12, and tumor necrosis factor-alpha, molecules playing a central role in the effector phase of macrophages. Our data indicate that (i) MIP-1alpha, MIP-1beta, RANTES, and ATAC are not only chemoattractants but also coactivators of macrophages, (ii) MIP-1alpha, MIP-1beta, RANTES, and ATAC constitute together with IFN-gamma a group of "type 1 cytokines," and (iii) these cytokines act together as a functional unit that is used by NK cells in the innate phase and then "handed over" to CD8(+) T cells in the antigen-specific phase of the immune defense, thus bridging the two components of a Th1 immune reaction. 相似文献
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Diagnosis and Differential Diagnosis of Ulcerative Colitis and Crohn's Disease by Hydrocolonic Sonography 总被引:2,自引:0,他引:2
Bernd Limberg M.D. Brigitte Osswald M.D. 《The American journal of gastroenterology》1994,89(7):1051-1057
Objectives: The entire length of the colon, starting at the rectosigmoid junction and ending at the cecum, can be visualized by transabdominal sonography after retrograde water instillation into the colon. By this method., termed hydrocolonic sonography, it is possible to evaluate in detail the lumen, the colon wall, and the surrounding tissue. Five layers of different echogenicity can be differentiated within the colon wall. Methods: In a prospective study of 440 patients, we compared the value of conventional ahdominal sonography and hydrocolonic sonography with that of colonoscopy, in the diagnosis and differential diagnosis of ulcerative colitis and colonic Crohn's disease. Results: In 93% of patients with Crohn's disease, the normal five-layer structure of the colonic wall was no longer in evidence, and the wall appeared hypoechogenic and clearly thickened. In contrast, in patients with ulcerative colitis, the five-layer structure could clearly be discerned, and although the colon wall remained hypoechogenic, it was only moderately thickened. Colonic Crohn's disease and ulcerative colitis were detectahle by hydrocolonic sonography, with a sensitivity of 96% and 917c, respectively, whereas the sensitivity achieved hy conventional abdominal sonography was only 71% and 62%, respectively. Furthermore, hydrocolonic sonography made possible the differentiation of Crohn's disease from ulcerative colitis in 93% of the cases. Conclusion: This new diagnostic procedure conld thus advantageously be introduced for the diagnosis, differential diagnosis, and follow-up of patients with chronic infiammatory large bowel diseases. 相似文献
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