PMID- 12239237
OWN - NLM
STAT- MEDLINE
DCOM- 20030307
LR  - 20190607
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 13
IP  - 10
DP  - 2002 Oct
TI  - Human platelets stimulate mesangial cells to produce monocyte chemoattractant 
      protein-1 via the CD40/CD40 ligand pathway and may amplify glomerular injury.
PG  - 2488-96
AB  - Platelets are thought to play an important role in the initiation and the 
      progression of a variety of glomerulonephritides. This study examined whether 
      platelets induce production of monocyte chemoattractant protein-1 (MCP-1), a 
      chemokine involved in leukocyte recruitment and glomerular injury, by cultured 
      human mesangial cells (MC). To this end, platelets isolated from normal human 
      donors were cocultured with MC at various ratios. MCP-1 synthesis was evaluated 
      by quantitative real-time PCR and enzyme-linked immunosorbent assay. Platelets at 
      1:100 ratio (MC to platelets) induced an approximately 20-fold increase in 
      mesangial MCP-1 mRNA and protein expression through an obligatory cell-to-cell 
      contact-dependent mechanism. Importantly, blockade of the CD40/CD40 ligand 
      (CD40L) pathway with neutralizing antibodies decreased MCP-1 production by 
      approximately 60%. It was confirmed that CD40 was functionally expressed on MC. 
      Gel-shift assays and inhibitors of phosphorylation were used to demonstrate that 
      activation of p38 mitogen-activated protein kinase, protein tyrosine kinases, and 
      nuclear factor-kappa B activation were essential for MCP-1 production. These data 
      indicate that platelet/MC contact stimulates the production of MCP-1 and may 
      contribute to glomerular inflammatory responses by recruiting leukocytes from the 
      peripheral blood.
FAU - Tanaka, Takaharu
AU  - Tanaka T
AD  - Third Department of Internal Medicine, Gunma University School of Medicine, 
      Maebashi, Gunma, Japan.
FAU - Kuroiwa, Takashi
AU  - Kuroiwa T
FAU - Ikeuchi, Hidekazu
AU  - Ikeuchi H
FAU - Ota, Fumie
AU  - Ota F
FAU - Kaneko, Yoriaki
AU  - Kaneko Y
FAU - Ueki, Kazue
AU  - Ueki K
FAU - Tsukada, Yoshito
AU  - Tsukada Y
FAU - McInnes, Iain B
AU  - McInnes IB
FAU - Boumpas, Dimitrios T
AU  - Boumpas DT
FAU - Nojima, Yoshihisa
AU  - Nojima Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 147205-72-9 (CD40 Ligand)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Blood Platelets/*physiology
MH  - CD40 Antigens/*metabolism
MH  - CD40 Ligand/*metabolism
MH  - Cell Communication
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis
MH  - Glomerular Mesangium/cytology/*metabolism/physiology
MH  - Glomerulonephritis/pathology
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/physiology
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2002/09/20 10:00
MHDA- 2003/03/08 04:00
CRDT- 2002/09/20 10:00
PHST- 2002/09/20 10:00 [pubmed]
PHST- 2003/03/08 04:00 [medline]
PHST- 2002/09/20 10:00 [entrez]
AID - 10.1097/01.asn.0000029588.07166.20 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2002 Oct;13(10):2488-96. doi: 
      10.1097/01.asn.0000029588.07166.20.