PMID- 11056009 OWN - NLM STAT- MEDLINE DCOM- 20001213 LR - 20220409 IS - 0021-9541 (Print) IS - 0021-9541 (Linking) VI - 185 IP - 3 DP - 2000 Dec TI - Downregulation of platelet-activating factor responsiveness during maturation of human dendritic cells. PG - 394-400 AB - Dendritic cells (DCs) are specialized antigen-presenting cells characterized by their ability to migrate into target sites, process antigens, and activate naive T-cells. Biological activities of platelet-activating factor (PAF) and the cytokine macrophage inflammatory protein-3beta (MIP-3beta) as well as the mRNA expression of their receptors were characterized in human DCs during lipopolysaccharide (LPS)-promoted maturation. Platelet-activating factor induced calcium transients, migration-associated actin polymerization response, and chemotaxis in immature human dendritic cells differentiated in vitro from monocytes with interleukin-4 and granulocyte macrophage colony stimulating factor. In addition, RT-PCR experiments indicated mRNA expression of the PAF receptor in these immature DCs. Cell studies and mRNA analyses further revealed that immature DCs neither respond to MIP-3beta nor express its specific receptor, CCR7. Induction of cell differentiation by LPS led to the loss of the mRNA expression of the PAF receptor, accompanied by decreasing intracellular calcium release, actin polymerization, and migration after stimulation with PAF. In contrast, LPS treatment induced increasing responsiveness toward MIP-3beta and mRNA expression of CCR7. Comparable data regarding mRNA expression of PAF receptor and PAF responsiveness were also obtained with another maturation protocol using TNFalpha instead of LPS. The direct comparison between the two different protocols showed a slower decrease of PAF responsiveness induced by TNFalpha than by LPS. These results show the loss of PAF responsiveness associated with downregulation of PAF receptor mRNA expression during LPS- and TNFalpha-induced maturation in human DCs. Therefore, these findings point to a functional relevance of PAF in recruiting immature DCs, whereas MIP-3beta might regulate the migration of DCs at a later stage of maturation. CI - Copyright 2000 Wiley-Liss, Inc. FAU - Dichmann, S AU - Dichmann S AD - Department of Experimental and Clinical Dermatology, University of Freiburg, Germany. dichmann@haut.ukl.uni-freiburg.de FAU - Rheinen, H AU - Rheinen H FAU - Panther, E AU - Panther E FAU - Herouy, Y AU - Herouy Y FAU - Czech, W AU - Czech W FAU - Termeer, C AU - Termeer C FAU - Simon, J C AU - Simon JC FAU - Gebicke-Haerter, P J AU - Gebicke-Haerter PJ FAU - Norgauer, J AU - Norgauer J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Platelet Activating Factor) RN - 0 (Platelet Membrane Glycoproteins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (platelet activating factor receptor) SB - IM MH - Antigen Presentation MH - Cell Differentiation/physiology MH - Cells, Cultured MH - Dendritic Cells/cytology/drug effects/*physiology MH - Humans MH - Platelet Activating Factor/*pharmacology/*physiology MH - Platelet Membrane Glycoproteins/*physiology MH - RNA, Messenger/analysis MH - *Receptors, Cell Surface MH - *Receptors, G-Protein-Coupled MH - Signal Transduction/drug effects/physiology EDAT- 2000/10/31 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/10/31 11:00 PHST- 2000/10/31 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/10/31 11:00 [entrez] AID - 10.1002/1097-4652(200012)185:3<394::AID-JCP9>3.0.CO;2-Z [pii] AID - 10.1002/1097-4652(200012)185:3<394::AID-JCP9>3.0.CO;2-Z [doi] PST - ppublish SO - J Cell Physiol. 2000 Dec;185(3):394-400. doi: 10.1002/1097-4652(200012)185:3<394::AID-JCP9>3.0.CO;2-Z.