title: The formyl peptide receptor like-1 and scavenger receptor MARCO are involved in glial cell activation in bacterial meningitis.
abstract: BACKGROUND
  Recent studies have suggested that the scavenger receptor MARCO (macrophage receptor with collagenous structure) mediates activation of the immune response in bacterial infection of the central nervous system (CNS). The chemotactic G-protein-coupled receptor (GPCR) formyl-peptide-receptor like-1 (FPRL1) plays an essential role in the inflammatory responses of host defence mechanisms and neurodegenerative disorders such as Alzheimer's disease (AD). Expression of the antimicrobial peptide cathelicidin CRAMP/LL-37 is up-regulated in bacterial meningitis, but the mechanisms underlying CRAMP expression are far from clear.
  
  
  METHODS
  Using a rat meningitis model, we investigated the influence of MARCO and FPRL1 on rCRAMP (rat cathelin-related antimicrobial peptide) expression after infection with bacterial supernatants of Streptococcus pneumoniae (SP) and Neisseria meningitides (NM). Expression of FPRL1 and MARCO was analyzed by immunofluorescence and real-time RT-PCR in a rat meningitis model. Furthermore, we examined the receptor involvement by real-time RT-PCR, extracellular-signal regulated kinases 1/2 (ERK1/2) phosphorylation and cAMP level measurement in glial cells (astrocytes and microglia) and transfected HEK293 cells using receptor deactivation by antagonists. Receptors were inhibited by small interference RNA and the consequences in NM- and SP-induced Camp (rCRAMP gene) expression and signal transduction were determined.
  
  
  RESULTS
  We show an NM-induced increase of MARCO expression by immunofluorescence and real-time RT-PCR in glial and meningeal cells. Receptor deactivation by antagonists and small interfering RNA (siRNA) verified the importance of FPRL1 and MARCO for NM- and SP-induced Camp and interleukin-1β expression in glial cells. Furthermore, we demonstrated a functional interaction between FPRL1 and MARCO in NM-induced signalling by real-time RT-PCR, ERK1/2 phosphorylation and cAMP level measurement and show differences between NM- or SP-induced signal transduction.
  
  
  CONCLUSIONS
  We propose that NM and SP induce glial cell activation and rCRAMP expression also via FPRL1 and MARCO. Thus the receptors contribute an important part to the host defence against infection.
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Germany.
authors.forename: Benedikt J
authors.initials: BJ
authors.lastname: Braun
authors.forename: Alexander
authors.initials: A
authors.lastname: Slowik
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Leib
authors.forename: Ralph
authors.initials: R
authors.lastname: Lucius
authors.forename: Deike
authors.initials: D
authors.lastname: Varoga
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Wruck
authors.forename: Sandra
authors.initials: S
authors.lastname: Jansen
authors.forename: Rainer
authors.initials: R
authors.lastname: Podschun
authors.forename: Thomas
authors.initials: T
authors.lastname: Pufe
authors.forename: Lars-Ove
authors.initials: LO
authors.lastname: Brandenburg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008578:Meninges / Q000166:cytology; D016920:Meningitis, Bacterial / Q000378:metabolism* / Q000382:microbiology; D009345:Neisseria meningitidis / Q000472:pathogenicity; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000235:genetics / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C105101:FPR2 protein, human; D053583:Interleukin-1beta; C490460:MARCO protein, human; C557529:MARCO protein, rat; D009842:Oligopeptides; D034741:RNA, Small Interfering; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; C509690:tryptophyl-arginyl-tryptophyl-tryptophyl-tryptophyl-tryptophanamide; D000242:Cyclic AMP; D037342:Pertussis Toxin; D048049:Extracellular Signal-Regulated MAP Kinases