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1.
Selective inhibition of T cell proliferation but not expression of effector function by human alveolar macrophages 总被引:1,自引:0,他引:1 下载免费PDF全文
BACKGROUND: Alveolar macrophages are thought to play an important part in regulating lung immune responses. While it is clear that human alveolar macrophages suppress T cell proliferation in vitro, the mechanisms by which this is achieved are not clear, nor is it known whether alveolar macrophages also inhibit other aspects of T cell function. METHODS: Peripheral blood mononuclear cells were stimulated with phytohaemagglutinin or house dust mite allergen, and cultured with variable numbers of autologous alveolar macrophages obtained by bronchoalveolar lavage from 20 normal subjects. RESULTS: Alveolar macrophages induced a reversible inhibition of T cell proliferation in response to both mitogen and allergen stimulation, with the latter being considerably more susceptible to inhibition. This was achieved via heterogenous mechanisms, involving both soluble factors derived from alveolar macrophages and cell-cell contact. Despite inhibiting proliferation, alveolar macrophages had little or no effect on T cell calcium flux, the characteristic changes in CD3, CD2, CD28 and interleukin-2 (IL-2) receptor expression which accompany normal T cell activation, and IL-2 and interferon gamma secretion. In contrast, alveolar macrophages inhibited the tyrosine phosphorylation of proteins which may be involved in IL-2 receptor-associated signal transduction. CONCLUSIONS: The immunoregulatory properties of alveolar macrophages are relatively selective, allowing T cell activation and cytokine secretion while inhibiting T cell proliferation within the lung.
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2.
Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells 总被引:7,自引:5,他引:7
Cell to cell communication via gap junctions is essential in the
maintenance of the homeostatic balance of multicellular organisms. Aberrant
intercellular gap junctional communication (GJIC) has been implicated in
tumor promotion, neuropathy and teratogenesis. Oxidative stress has also
been implicated in similar pathologies such as cancer. We report a
potential link between oxidative stress and GJIC. Hydrogen peroxide, a
known tumor promoter, inhibited GJIC in WB-F344 rat liver epithelial cells
with an I50 value of 200 microM. Inhibition of GJIC by H2O2 was reversible
as indicated by the complete recovery of GJIC with the removal of H2O2 via
a change of fresh media. Free radical scavengers, such as t-butyl alcohol,
propylgallate, and Trolox, did not prevent the inhibition of GJIC by H2O2,
which indicated that the effects of H2O2 on GJIC was probably not a
consequence of aqueous free radical damage. The depletion of intracellular
GSH reversed the inhibitory effect of H2O2 on GJIC. The treatment of
glutathione- sufficient cells with H2O2 resulted in the
hyperphosphorylation of connexin43, which is the basic subunit of the
hexameric gap junction protein, as determined by Western blot analysis.
TPA, a well-known tumor promoter, also inhibits GJIC via
hyperphosphorylation of GJIC, which is a result of protein kinase-C
activation. However, H2O2 also induced hyperphosphorylation in
GSH-deficient cells that had normal rates of GJIC. Therefore, the mechanism
of GJIC inhibition must be different from the TPA-pathway and involves GSH.
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S. A. Hiles E. S. Harvey V. M. McDonald M. Peters P. Bardin P. N. Reynolds J. W. Upham M. Baraket Z. Bhikoo J. Bowden B. Brockway L. P. Chung B. Cochrane G. Foxley J. Garrett M. Hew L. Jayaram C. Jenkins C. Katelaris G. Katsoulotos M. S. Koh V. Kritikos M. Lambert D. Langton A. Lara Rivero G. B. Marks P. G. Middleton A. Nanguzgambo N. Radhakrishna H. Reddel J. Rimmer A. M. Southcott M. Sutherland F. Thien P. A. B. Wark I. A. Yang E. Yap P. G. Gibson 《Clinical and experimental allergy》2018,48(6):650-662
5.
Slonimsky Einat Upham Kent Pepley Sarah Ouyang Tao King Tonya Fiorelli Marco Thamburaj Krishnamoorthy 《Emergency radiology》2022,29(3):427-435
Emergency Radiology - In subarachnoid hemorrhage, noncontrast CT features are used to guide the localization of ruptured aneurysms on CT angiography and DSA. Multiplanar CT may improve the... 相似文献
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