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The formyl peptide receptor like-1 and scavenger receptor MARCO are involved in glial cell activation in bacterial meningitis.

Braun BJ, Slowik A, Leib SL, Lucius R, Varoga D, Wruck CJ, Jansen S, Podschun R, Pufe T, Brandenburg LO - J Neuroinflammation (2011)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Germany.

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.

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Neisseria meningitides bacterial supernatants induced an increase of MARCO immunoreactivity in astrocytes. Primary rat astrocytes and microglia were fixed and labelled with anti-FPRL1 and anti-MARCO antibodies. FPRL1 (A) and MARCO (B) protein expression was examined by immunofluorescence microscopy. Bisbenzimide was used for nuclear counter-staining (blue). The figures show representative results from one of three independent experiments. Scale bar: 20 μm.
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Figure 2: Neisseria meningitides bacterial supernatants induced an increase of MARCO immunoreactivity in astrocytes. Primary rat astrocytes and microglia were fixed and labelled with anti-FPRL1 and anti-MARCO antibodies. FPRL1 (A) and MARCO (B) protein expression was examined by immunofluorescence microscopy. Bisbenzimide was used for nuclear counter-staining (blue). The figures show representative results from one of three independent experiments. Scale bar: 20 μm.

Mentions: We then examined the FPRL1 and MARCO expression in primary rat astrocytes and microglia cells after treatment with NM and SP bacterial supernatants for 24 h using fluorescence microscopy. For FPRL1, both primary cells showed a clearly protein expression, but NM as well as SP could not induce an increased receptor expression (Figure 2A). For MARCO, we could detect an increase of protein expression in astrocytes after NM treatment, whereas SP induced no change of receptor expression in astrocytes as well as microglia (Figure 2B).


The formyl peptide receptor like-1 and scavenger receptor MARCO are involved in glial cell activation in bacterial meningitis.

Braun BJ, Slowik A, Leib SL, Lucius R, Varoga D, Wruck CJ, Jansen S, Podschun R, Pufe T, Brandenburg LO - J Neuroinflammation (2011)

Neisseria meningitides bacterial supernatants induced an increase of MARCO immunoreactivity in astrocytes. Primary rat astrocytes and microglia were fixed and labelled with anti-FPRL1 and anti-MARCO antibodies. FPRL1 (A) and MARCO (B) protein expression was examined by immunofluorescence microscopy. Bisbenzimide was used for nuclear counter-staining (blue). The figures show representative results from one of three independent experiments. Scale bar: 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3040686&req=5

Figure 2: Neisseria meningitides bacterial supernatants induced an increase of MARCO immunoreactivity in astrocytes. Primary rat astrocytes and microglia were fixed and labelled with anti-FPRL1 and anti-MARCO antibodies. FPRL1 (A) and MARCO (B) protein expression was examined by immunofluorescence microscopy. Bisbenzimide was used for nuclear counter-staining (blue). The figures show representative results from one of three independent experiments. Scale bar: 20 μm.
Mentions: We then examined the FPRL1 and MARCO expression in primary rat astrocytes and microglia cells after treatment with NM and SP bacterial supernatants for 24 h using fluorescence microscopy. For FPRL1, both primary cells showed a clearly protein expression, but NM as well as SP could not induce an increased receptor expression (Figure 2A). For MARCO, we could detect an increase of protein expression in astrocytes after NM treatment, whereas SP induced no change of receptor expression in astrocytes as well as microglia (Figure 2B).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Germany.

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.

Show MeSH
Related in: MedlinePlus