1,161 research outputs found

    Nucleotides Regulate Secretion of the Inflammatory Chemokine CCL2 from Human Macrophages and Monocytes

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    CCL2 is an important inflammatory chemokine involved in monocyte recruitment to inflamed tissues. The extracellular nucleotide signalling molecules UTP and ATP acting via the P2Y2 receptor are known to induce CCL2 secretion in macrophages. We confirmed this in the human THP-1 monocytic cell line showing that UTP is as efficient as LPS at inducing CCL2 at early time points (2–6 hours). Expression and calcium mobilisation experiments confirmed the presence of functional P2Y2 receptors on THP-1 cells. UTP stimulation of human peripheral CD14+ monocytes showed low responses to LPS (4-hour stimulation) but a significant increase above background following 6 hours of treatment. The response to UTP in human monocytes was variable and required stimulation >6 hours. With such variability in response we looked for single nucleotide polymorphisms in P2RY2 that could affect the functional response. Sequencing of P2RY2 from THP-1 cells revealed the presence of a single nucleotide polymorphism altering amino acid 312 from arginine to serine (rs3741156). This polymorphism is relatively common at a frequency of 0.276 ( subjects). Finally, we investigated CCL2 secretion in response to LPS or UTP in human macrophages expressing 312Arg-P2Y2 or 312Ser-P2Y2 where only the latter exhibited significant UTP-induced CCL2 secretion ( donors per group)

    Induced gravitational collapse at extreme cosmological distances: the case of GRB 090423

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    CONTEXT: The induced gravitational collapse (IGC) scenario has been introduced in order to explain the most energetic gamma ray bursts (GRBs), Eiso=10^{52}-10^{54}erg, associated with type Ib/c supernovae (SNe). It has led to the concept of binary-driven hypernovae (BdHNe) originating in a tight binary system composed by a FeCO core on the verge of a SN explosion and a companion neutron star (NS). Their evolution is characterized by a rapid sequence of events: [...]. AIMS: We investigate whether GRB 090423, one of the farthest observed GRB at z=8.2, is a member of the BdHN family. METHODS: We compare and contrast the spectra, the luminosity evolution and the detectability in the observations by Swift of GRB 090423 with the corresponding ones of the best known BdHN case, GRB 090618. RESULTS: Identification of constant slope power-law behavior in the late X-ray emission of GRB 090423 and its overlapping with the corresponding one in GRB 090618, measured in a common rest frame, represents the main result of this article. This result represents a very significant step on the way to using the scaling law properties, proven in Episode 3 of this BdHN family, as a cosmological standard candle. CONCLUSIONS: Having identified GRB 090423 as a member of the BdHN family, we can conclude that SN events, leading to NS formation, can already occur already at z=8.2, namely at 650 Myr after the Big Bang. It is then possible that these BdHNe originate stem from 40-60 M_{\odot} binaries. They are probing the Population II stars after the completion and possible disappearance of Population III stars.Comment: 9 pages, 9 figures, to appear on A&
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