+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Cyclic ADP-ribose is a second messenger in the lipopolysaccharide-stimulated proliferation of human peripheral blood mononuclear cells

, : Cyclic ADP-ribose is a second messenger in the lipopolysaccharide-stimulated proliferation of human peripheral blood mononuclear cells. Biochemical Journal 375(Pt 2): 395-403

Cyclic ADP-ribose (cADPR), a universal calcium mobilizer from intracellular stores, was recently demonstrated to stimulate proliferation of various cell types. The role of cADPR in a specific process of monocyte- and plasma-mediated activation of T-lymphocytes by lipopolysaccharide (LPS) was addressed using human mononuclear cells from peripheral blood (PBMCs). Incubation of PBMCs with 0.1 microg/ml of LPS for 24 h provided a doubling in the intracellular levels of cADPR as compared with unstimulated PBMCs. The cADPR increase was abolished either by prior removal of monocytes or by pre-incubating a whole PBMC population with a monoclonal antibody against the monocyte marker CD14. The increased concentrations of intracellular cADPR elicited by LPS stimulation were paralleled by significant increases in NAD+ levels and in the activities of ectocellular and membrane-bound fractions of ADP-ribosyl cyclase/cADPR hydrolase activities. A cytosolic ADP-ribosyl cyclase was also detectable in PBMCs and its activity was comparably enhanced by LPS stimulation. This soluble cyclase is distinguished from the membrane-bound cyclase by both substrate and inhibitor sensitivities. LPS-stimulated PBMCs showed 2-3-fold increases of intracellular calcium ([Ca2+]i), and these changes were prevented completely by the cADPR antagonist 8-Br-cADPR and by ryanodine. Both compounds, and the cyclase inhibitor nicotinamide, significantly inhibited the T-lymphocyte proliferation induced by LPS in PBMCs. These results demonstrate that cADPR plays a role of second messenger in the adaptive immune recognition process of LPS-stimulated proliferation of PBMCs.


PMID: 12852785

DOI: 10.1042/BJ20030556

Other references

Philippidou, P.; Valdez, G.; Akmentin, W.; Bowers, W.J.; Federoff, H.J.; Halegoua, S., 2011: Trk retrograde signaling requires persistent, Pincher-directed endosomes. Target-derived neurotrophins use retrogradely transported Trk-signaling endosomes to promote survival and neuronal phenotype at the soma. Despite their critical role in neurotrophin signaling, the nature and molecular composition of these endosome...

Rausch, N.G., 1949: Five-day ambulatory penicillin therapy of early syphilis. New York State Journal of Medicine 49(14): 1668-1670

Iio, M., 1971: Further observation on 131 I-BSP clearance in the Dubin-Johnson syndrome. Journal of Nuclear Medicine 12(11): 768-768

Wang E.; Merrill A.H.Jr; Norred W.P.; Bacon C.; Riley R.T., 1991: Inhibition of sphingosine biosynthesis by fumonisins mycotoxins produced by fusarium moniliforme. FASEB Journal 5(6): A1605

Svedman P.; Jacobsson S.; Lindell S.E.; Ponnert L., 1978: Measurement of trans cutaneous oxygen tension a method for studying the blood supply to the skin. IRCS (International Research Communications System) Medical Science Library Compendium 6(8): 339

Eichenberger, A.P.; van Gunsteren, W.F.; Smith, L.J., 2013: Structure of hen egg-white lysozyme solvated in TFE/water: a molecular dynamics simulation study based on NMR data. Various experimental studies of hen egg white lysozyme (HEWL) in water and TFE/water clearly indicate structural differences between the native state and TFE state of HEWL, e.g. the helical content of the protein in the TFE state is much higher th...

Marotti, G., 1961: Modificazioni strutturali ed istochimiche della cornea dell'embrione di polio in bulbi oculari sperimentalrnente ridotti. Atti della Societa Italiana di Anatomia, 21: 290-293

Yuksel, D.; Ozer, Pınar.Altiaylik., 2014: Long-term results of probing guided with soft cannula in children with congenital nasolacrimal duct obstruction. To report the results of soft probing in children with congenital nasolacrimal duct obstruction (CNLDO). A prospective, non-randomised interventional study included 158 eyes of 122 children aged 2 months-5 years, with CNLDO. A plastic intravenous...

Zagórska, L.; Chroboczek, J.; Zagórski, W., 1975: Template activity of complexes formed between bacteriophage f2 RNA and coat protein. Formation of complexes between f2 RNA polymerase cistron was partially inhibited, some RNA and coat protein was studied using salt conditions which are optimum for phage protein synthesis. In this ionic environment, coat protein precipitation can...

Shitara, K.; Kuwana, Y.; Nakamura, K.; Tokutake, Y.; Ohta, S.; Miyaji, H.; Hasegawa, M.; Hanai, N., 1993: A mouse/human chimeric anti-(ganglioside GD3) antibody with enhanced antitumor activities. Ganglioside GD3, which is one of the major gangliosides expressed on the cell surface of human tumors of neuroectodermal origin has been focused on as a target molecule for passive immunotherapy. We have cloned the cDNA encoding the immunoglobulin...