PMID- 11440636
OWN - NLM
STAT- MEDLINE
DCOM- 20010927
LR  - 20211203
IS  - 1079-9907 (Print)
IS  - 1079-9907 (Linking)
VI  - 21
IP  - 6
DP  - 2001 Jun
TI  - An anti-inflammatory drug, propagermanium, may target GPI-anchored proteins 
      associated with an MCP-1 receptor, CCR2.
PG  - 389-98
AB  - Monocyte chemoattractant protein-1 (MCP-1) promotes the migration and activation 
      of monocytes and plays a pivotal role in the development of chronic inflammation. 
      Propagermanium (3-oxygermylpropionic acid polymer) has been used as a therapeutic 
      agent against chronic hepatitis B in Japan. We report here that propagermanium 
      specifically inhibits in vitro chemotactic migration of monocytes by MCP-1. 
      Propagermanium did not inhibit binding of MCP-1 to a human monocytic cell line, 
      THP-1 cells, or affect intracellular Ca(2+) mobilization or the cAMP 
      concentration in MCP-1-treated THP-1 cells. The effect of propagermanium seems to 
      require glycosylphosphatidylinositol (GPI)-anchored proteins, as cleavage of GPI 
      anchors by phosphatidylinositol-phospholipase C (PI-PLC) eliminated the 
      inhibitory activity of propagermanium. Anti-GPI-anchored protein antibodies, such 
      as anti-CD55 and anti-CD59, reduced staining of C-C chemokine receptor 2 (CCR2) 
      with an anti-CCR2 antibody against the N-terminus of CCR2 in a flow cytometric 
      analysis, and these antibodies also selectively inhibited MCP-1-induced migration 
      of THP-1 cells. Furthermore, under fluorescence microscopy, GPI-anchored proteins 
      colocalized with CCR2 on THP-1 cells. These results suggest that propagermanium 
      may target GPI-anchored proteins that are closely associated with CCR2 to 
      selectively inhibit the MCP-1-induced chemotaxis, thus providing a mechanistic 
      basis for the anti-inflammatory effects of the drug.
FAU - Yokochi, S
AU  - Yokochi S
AD  - Central Research Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd., Hokusei-cho, 
      Inabe-gun, Mie 511-0406, Japan.
FAU - Hashimoto, H
AU  - Hashimoto H
FAU - Ishiwata, Y
AU  - Ishiwata Y
FAU - Shimokawa, H
AU  - Shimokawa H
FAU - Haino, M
AU  - Haino M
FAU - Terashima, Y
AU  - Terashima Y
FAU - Matsushima, K
AU  - Matsushima K
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the 
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (CCR2 protein, human)
RN  - 0 (CD55 Antigens)
RN  - 0 (Glycoproteins)
RN  - 0 (Glycosylphosphatidylinositols)
RN  - 0 (Integrin alphaXbeta2)
RN  - 0 (Organometallic Compounds)
RN  - 0 (Propionates)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 00072J7XWS (Germanium)
RN  - 1Q2P9TO9Q7 (propagermanium)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Binding Sites
MH  - CD55 Antigens/metabolism
MH  - Cell Line
MH  - Chemotaxis, Leukocyte/drug effects
MH  - Germanium
MH  - Glycoproteins/*metabolism
MH  - Glycosylphosphatidylinositols/*metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Integrin alphaXbeta2/metabolism
MH  - Organometallic Compounds/*pharmacology
MH  - Propionates
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/chemistry/*metabolism
EDAT- 2001/07/07 10:00
MHDA- 2001/09/28 10:01
CRDT- 2001/07/07 10:00
PHST- 2001/07/07 10:00 [pubmed]
PHST- 2001/09/28 10:01 [medline]
PHST- 2001/07/07 10:00 [entrez]
AID - 10.1089/107999001750277862 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 2001 Jun;21(6):389-98. doi: 
      10.1089/107999001750277862.