PMID- 17192399 OWN - NLM STAT- MEDLINE DCOM- 20070605 LR - 20220129 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 109 IP - 9 DP - 2007 May 1 TI - Stimulation of P2 receptors causes release of IL-1beta-loaded microvesicles from human dendritic cells. PG - 3856-64 AB - Dendritic cells (DCs) are professional antigen-presenting cells that initiate the immune response by activating T lymphocytes. DCs express plasma membrane receptors for extracellular nucleotides named P2 receptors (P2Rs). Stimulation of P2Rs in these cells is known to cause chemotaxis, cytokine release, and cell death and to modulate LPS-dependent differentiation. Here we show that stimulation of the P2X(7) receptor subtype (P2X(7)R) causes fast microvesicle shedding from DC plasma membrane. Vesicle release occurs from both immature and mature DCs; however, only vesicles from mature DCs, due to their previous exposure to LPS, contain IL-1beta. Microvesicles, whether from immature or mature DCs, also contain caspase-1 and -3 and cathepsin D. They also express the P2X(7)R in addition to other P2Rs and known markers of immune cells such as major histocompatibility complex II (MHC II) and CD39. Activation of the P2X(7)R by extracellular ATP causes IL-1beta release from the vesicle lumen. Previous studies demonstrated that high extracellular K(+) inhibits IL-1beta processing and release; here we show that high ionic strength reduces microvesicle shedding when compared with a low ionic strength medium but strongly increases microvesicle IL-1beta loading. FAU - Pizzirani, Cinzia AU - Pizzirani C AD - Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, I-44100 Ferrara, Italy. FAU - Ferrari, Davide AU - Ferrari D FAU - Chiozzi, Paola AU - Chiozzi P FAU - Adinolfi, Elena AU - Adinolfi E FAU - Sandona, Dorianna AU - Sandona D FAU - Savaglio, Erika AU - Savaglio E FAU - Di Virgilio, Francesco AU - Di Virgilio F LA - eng GR - GGP06070/TI_/Telethon/Italy PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061227 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Interleukin-1beta) RN - 0 (Lipopolysaccharides) RN - 0 (P2RX7 protein, human) RN - 0 (Purinergic P2 Receptor Agonists) RN - 0 (Receptors, Purinergic P2) RN - 0 (Receptors, Purinergic P2X7) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.36 (Caspase 1) RN - EC 3.4.23.5 (Cathepsin D) RN - RWP5GA015D (Potassium) SB - IM MH - Adenosine Triphosphate/*pharmacology MH - Caspase 1/immunology/metabolism MH - Caspase 3/immunology/metabolism MH - Cathepsin D/immunology/metabolism MH - Cell Differentiation/drug effects/immunology MH - Cells, Cultured MH - Dendritic Cells/cytology/immunology/*metabolism MH - Humans MH - Interleukin-1beta/immunology/*metabolism MH - Lipopolysaccharides/pharmacology MH - Potassium/immunology/metabolism MH - Purinergic P2 Receptor Agonists MH - Receptors, Purinergic P2/immunology/*metabolism MH - Receptors, Purinergic P2X7 MH - Secretory Vesicles/immunology/*metabolism EDAT- 2006/12/29 09:00 MHDA- 2007/06/06 09:00 CRDT- 2006/12/29 09:00 PHST- 2006/12/29 09:00 [pubmed] PHST- 2007/06/06 09:00 [medline] PHST- 2006/12/29 09:00 [entrez] AID - S0006-4971(20)41633-7 [pii] AID - 10.1182/blood-2005-06-031377 [doi] PST - ppublish SO - Blood. 2007 May 1;109(9):3856-64. doi: 10.1182/blood-2005-06-031377. Epub 2006 Dec 27.