@entity19396 (cADPR), a universal @entity460 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 @entity1 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 @entity5750 . 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 @entity857 - @entity13338 cyclase/cADPR hydrolase activities. A cytosolic @entity857 - @entity13338 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 @entity460 ([ @entity141 ]i), and these changes were prevented completely by the cADPR antagonist @entity69204 and by @entity8452 . Both compounds, and the cyclase inhibitor @entity4571 , 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.

XXXX is a second messenger in the lipopolysaccharide-stimulated proliferation of @entity1 peripheral blood mononuclear cells.

@entity1 :: ('9606', 'Species') :: ['human'] @entity5750 :: ('929', 'Gene') :: ['CD14'] @entity8452 :: ('MESH:D012433', 'Chemical') :: ['ryanodine'] @entity13338 :: ('CHEBI:26565', 'Chemical') :: ['ribosyl'] @entity19396 :: ('MESH:D036563', 'Chemical') :: ['Cyclic ADP-ribose'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity857 :: ('MESH:D000244', 'Chemical') :: ['ADP'] @entity4571 :: ('MESH:D009536', 'Chemical') :: ['nicotinamide'] @entity69204 :: ('MESH:C493642', 'Chemical') :: ['8-Br-cADPR']
@entity19396 :: (MESH:D036563,Chemical) :: ['Cyclic ADP-ribose']
