Article

The collagen-breakdown product N-acetyl-Proline-Glycine-Proline (N-alpha-PGP) does not interact directly with human CXCR1 and CXCR2.

Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
European journal of pharmacology (Impact Factor: 2.59). 09/2010; 643(1):29-33. DOI: 10.1016/j.ejphar.2010.06.017
Source: PubMed

ABSTRACT Neutrophils transmigrate from the blood into inflamed tissue via the interaction of chemokines produced in this tissue with chemokine receptors, such as CXCR1 and CXCR2, that are expressed on the membranes of neutrophils. Subsequently, activation of neutrophils will in turn lead to increased tissue damage and thereby enhanced clinical symptoms of inflammatory diseases like chronic obstructive pulmonary disease, inflammatory bowel disease and psoriasis. Besides chemokines, also the collagen-breakdown product N-acetyl-Proline-Glycine-Proline (N-alpha-PGP) attracts neutrophils. In a recent article (Weathington et al., 2006) it was suggested that N-alpha-PGP exerts its effect via CXCR1 and CXCR2. In this study, we show that N-alpha-PGP, in contrast to CXCL8, does not directly activate or interact with CXCR1 or CXCR2. N-alpha-PGP was not able to displace the radioligand [(125)I]CXCL8 from CXCR1 and CXCR2 expressing HEK293T cells or neutrophils. In addition, N-alpha-PGP did not displace the radioligand [(3)H]-SB265610, a CXCR2 antagonist, from CXCR2 expressing cells. Furthermore, N-alpha-PGP was not able to activate G protein signalling in cells expressing CXCR1 and CXCR2. N-alpha-PGP was also not able to recruit beta-arrestin2, an intracellular scaffolding protein involved in G protein-independent signalling, in cells expressing CXCR2. These studies indicate that N-alpha-PGP is not a ligand of CXCR1 or CXCR2.

0 Bookmarks
 · 
230 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: In France, the majority of the electricity generated is derived from nuclear energy which has a low CO2 footprint.A preliminary analysis showed us that, in the French specific context, without any new nuclear power plant construction, the emission of several millions tons of CO2 could be avoided by using a CO2 to fuel technology to adjust the electricity produced by nuclear energy to the electricity grid demand. This will not only mitigate CO2 emissions but could also increase nuclear economic competitiveness.Possibilities of direct using nuclear heat are also under investigation, to improve the efficiency of the global system of conversion.
    Energy Procedia 01/2011; 4:2113-2120.
  • Blood 02/2013; 121(9):1489-91. · 9.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Considerable effort on research in CO2 capture technologies has been directed towards steady state systems while less seems to have been done for the same systems in transient state. This work presents a dynamic model for CO2 absorption using aqueous mono-ethanolamine (MEA). Validation against experimental results both obtained at steady state and dynamic conditions is included. A parametric sensitivity study of the underlying model equations is carried out based alternative parameter correlations for the reaction rate constant. It is concluded that validated results for one specific pilot plant don’t necessarily apply to other plants of different sizes under other operational conditions. Furthermore, a parametric sensitivity study for the other parameters as well as for the rest of the CO2 capture process is also warranted.
    Energy Procedia 01/2011; 4:1526-1533.