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Intercellular Mediators (intercellular + mediator)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Neurone-to-astrocyte communication by endogenous ATP in mixed culture of rat hippocampal neurones and astrocytes

DRUG DEVELOPMENT RESEARCH, Issue 1 2003
Schuichi Koizumi
ATP is recognized as an important intercellular signaling molecule in the peripheral and CNS. Glutamate is reported to be an important neurone-to-glia mediator being released from neurones and astrocytes that activates astrocytic and neuronal Ca2+ responses, respectively. We demonstrate here that endogenous ATP could be an extracellular molecule for neurone-to-astrocyte communication in cocultured rat hippocampal neurones and astrocytes. Hippocampal neurones reveal synchronized Ca2+ oscillation, which was due to glutamatergic synaptic transmission. When analyzed in a fura-2 method, a slight and very slow increase in intracellular Ca2+ concentration ([Ca2+]i) elevation was observed in some population of astrocytes. Such astrocytic [Ca2+]i elevation was dramatically inhibited by apyrase, though apyrase itself had no effect on neuronal Ca2+ oscillation. For a detail analysis, we investigated changes in [Ca2+]i in cells using a confocal microscopy. When cocultured hippocampal neurones and astrocytes were depolarized electronically in the presence of glutamate-receptor antagonists, a transient elevation in [Ca2+]i was observed in neurones, which was followed by a slowly initiated and small rise in [Ca2+]i in astrocytes. Apyrase or P2 receptor antagonists almost abolished the [Ca2+]i rises in astrocytes, suggesting that depolarization-evoked ATP release from neurones should produce astrocytic [Ca2+]i elevation via P2 receptors. Using a luciferin,luciferase bioluminescence assay, we found that neurones could release ATP in an activity-dependent manner. These findings suggest that endogenous ATP should be an important intercellular mediator between neurones and astrocytes and that functions of these cells should be fine-tuned by endogenously released ATP in situ. Drug Dev. Res. 59:88,94, 2003. © 2003 Wiley-Liss, Inc. [source]

Extracellular vesicles are key intercellular mediators in the development of immune dysfunction to allergens in the airways

ALLERGY, Issue 10 2010
T.-S. Shin
To cite this article: Shin T-S, Kim JH, Kim Y-S, Jeon SG, Zhu Z, Gho YS, Kim Y-K. Extracellular vesicles are key intercellular mediators in the development of immune dysfunction to allergens in the airways. Allergy 2010; 65: 1256,1265. Abstract Background:, Previous evidence indicates that inhalation of lipopolysaccharide (LPS)-containing with allergens induced mixed Th1 and Th17 cell responses in the airways. Extracellular vesicles (EVs) are nanometer-sized spherical, lipid-bilayered structures and are recently in the public eye as an intercellular communicator in immune responses. Objective:, To evaluate the role of EVs secreted by LPS inhalation in the development of airway immune dysfunction in response to allergens. Methods:, Extracellular vesicles in bronchoalveolar lavage fluids of BALB/c mice were isolated and characterized 24 h after applications to the airway of 10 ,g of LPS for 3 days. To evaluate the role of LPS-induced EVs on the development of airway immune dysfunction, in vivo and in vitro experiments were performed using the isolated LPS-induced EVs. Results:, The inhalation of LPS enhanced EVs release into the BAL fluid, when compared to the application of PBS. Airway sensitization with allergens and LPS-induced EVs resulted in a mixed Th1 and Th17 cell responses, although that with allergens and PBS-induced EVs induced immune tolerance. In addition, LPS-induced EVs enhanced the production of Th1- and Th17-polarizing cytokines (IL-12p70 and IL-6, respectively) by lung dendritic cells. Moreover, the immune responses induced by the LPS-induced EVs were blocked by denaturation of the EV-bearing proteins. Conclusion:, These data suggest that EVs (especially, the protein components) secreted by LPS inhalation are a key intercellular communicator in the development of airway immune dysfunction to inhaled LPS-containing allergens. [source]

Prostaglandins, bioassay and inflammation

BRITISH JOURNAL OF PHARMACOLOGY, Issue S1 2006
R J Flower
The formation of the British Pharmacological Society coincided almost exactly with a series of ground-breaking studies that ushered in an entirely new field of research , that of lipid mediator pharmacology. For many years following their chemical characterisation, lipids were considered only to be of dietary or structural importance. From the 1930s, all this changed , slowly at first and then more dramatically in the 1970s and 1980s with the emergence of the prostaglandins (PGs), the first intercellular mediators to be clearly derived from lipids, in a dynamic on-demand system. The PGs exhibit a wide range of biological activities that are still being evaluated and their properties underlie the action of one of the world's all-time favourite medicines, aspirin, as well as its more modern congeners. This paper traces the development of the PG field, with particular emphasis on the skilful utilisation of the twin techniques of bioassay and analytical chemistry by U.K. and Swedish scientists, and the intellectual interplay between them that led to the award of a joint Nobel Prize to the principal researchers in the PG field, half a century after the first discovery of these astonishingly versatile mediators. British Journal of Pharmacology (2006) 147, S182,S192. doi:10.1038/sj.bjp.0706506 [source]