PMID- 11412312
OWN - NLM
STAT- MEDLINE
DCOM- 20010719
LR  - 20240413
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 103
IP  - 2
DP  - 2001 Jun
TI  - The pan-chemokine inhibitor NR58-3.14.3 abolishes tumour necrosis factor-alpha 
      accumulation and leucocyte recruitment induced by lipopolysaccharide in vivo.
PG  - 244-54
AB  - Chemokines participate in the regulation of leucocyte recruitment in a wide 
      variety of inflammatory processes, including host defence and diseases such as 
      asthma, atherosclerosis and autoimmune disorders. We have previously described 
      the properties of Peptide 3, the first broad-specificity chemokine inhibitor in 
      vitro. Here, we report the properties of NR58-3.14.3, a retroinverso analogue of 
      Peptide 3. NR58-3.14.3 inhibited leucocyte migration induced by a range of 
      chemokines, including monocyte chemoattractant protein-1 (MCP-1) (2.5 nM), 
      macrophage inflammatory protein-1alpha (MIP-1alpha) (5 nM), regulated on 
      activation, normal T-cell expressed and presumably secreted (RANTES) (20 nM), 
      stromal cell-derived factor-1alpha (SDF-1alpha) (25 nM) and interleukin-8 (IL-8) 
      (30 nM), but did not affect migration induced by 
      N-formyl-methionyl-leucyl-phenylalanine (FMLP) or complement C5a (> 100 microM). 
      NR58-3.14.3 is therefore approximately 1000-fold more potent than Peptide 3 but 
      retains the broad-spectrum chemokine inhibitory activity of the parent peptide. 
      In vivo, pretreatment with a systemic dose of 10 mg of NR58-3.14.3, but not the 
      inactive derivative NR58-3.14.4, abolished leucocyte recruitment in response to 
      intradermal injection of 500 ng of MCP-1 into rat skin. This suggests that 
      NR58-3.14.3 is a functional chemokine inhibitor in vivo as well as in vitro. We 
      utilized NR58-3.14.3 as a tool to investigate the role of chemokine activity 
      during leucocyte recruitment in response to lipopolysaccharide (LPS) in vivo. 
      NR58-3.14.3, but not NR58-3.14.4, abolished leucocyte recruitment in response to 
      intradermal injection of 50 ng of LPS into rat skin. Furthermore, NR58-3.14.3 
      completely inhibited LPS-induced accumulation of tumour necrosis factor-alpha 
      (TNF-alpha). This data is consistent with a model in which multiple chemokines 
      act in parallel upstream of TNF-alpha. NR58-3.14.3 is therefore a powerful 
      anti-inflammatory agent in vivo, suppressing proinflammatory cytokine production 
      and leucocyte recruitment in response to endotoxin stimulus in rat skin.
FAU - Reckless, J
AU  - Reckless J
AD  - Department of Medicine, University of Cambridge, Addenbrooke's Hospital, 
      Cambridge, UK. jr219@mole.bio.cam.ac.uk
FAU - Tatalick, L M
AU  - Tatalick LM
FAU - Grainger, D J
AU  - Grainger DJ
LA  - eng
PT  - Journal Article
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 
      (cyclo(cysteinyl-glutaminyl-isoleucyl-tryptophyl-lysyl-glutaminyl-lysyl-prolyl-aspartyl-leucyl-cysteinyl-amide))
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/antagonists & inhibitors/immunology
MH  - Chemokines/antagonists & inhibitors
MH  - Dermatitis/immunology/*prevention & control
MH  - Drug Design
MH  - Female
MH  - Humans
MH  - Leukocytes/*immunology
MH  - Lipopolysaccharides/*antagonists & inhibitors/immunology
MH  - Peptides, Cyclic/chemistry/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stereoisomerism
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*immunology
PMC - PMC1783230
EDAT- 2001/06/20 10:00
MHDA- 2001/07/20 10:01
PMCR- 2002/06/01
CRDT- 2001/06/20 10:00
PHST- 2001/06/20 10:00 [pubmed]
PHST- 2001/07/20 10:01 [medline]
PHST- 2001/06/20 10:00 [entrez]
PHST- 2002/06/01 00:00 [pmc-release]
AID - imm1228 [pii]
AID - 10.1046/j.1365-2567.2001.01228.x [doi]
PST - ppublish
SO  - Immunology. 2001 Jun;103(2):244-54. doi: 10.1046/j.1365-2567.2001.01228.x.