Lysophospholipids increase ICAM-1 expression in HUVEC through a Gi- and NF-kappaB-dependent mechanism.
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S-1-P) are both low molecular weight lysophospholipid (LPL) ligands that are recognized by the Edg family of G protein-coupled receptors. In endothelial cells, these two ligands activate Edg receptors, resulting in cell proliferation and cell migration. The intercellular adhesion molecule-1 (ICAM-1, CD54) is one of many cell adhesion molecules belonging to the immunoglobulin superfamily. This study showed that LPA and S-1-P enhance ICAM-1 expression at both the mRNA and protein levels in human umbilical cord vein endothelial cells (HUVECs). This enhanced ICAM-1 expression in HUVECs was first observed at 2 h postligand treatment. Maximal expression appeared at 8 h postligand treatment, as detected by flow cytometry and Western blotting. Furthermore, the effects of S-1-P on ICAM-1 expression were shown to be concentration dependent. Prior treatment of HUVECs with pertussis toxin, a specific inhibitor of G(i), ammonium pyrrolidinedithiocarbamate and BAY 11-7082, inhibitors of the nuclear factor (NF)-kappaB pathway, or Clostridium difficile toxin B, an inhibitor of Rac, prevented the enhanced effect of LPL-induced ICAM-1 expression. However, pretreatment of HUVECs with exoC3, an inhibitor of Rho, had no effect on S-1-P-enhanced ICAM-1 expression. In a static cell-cell adhesion assay system, pretreatment of LPL enhanced the adhesion between HUVECs and U-937 cells, a human mononucleated cell line. The enhanced adhesion effect could be prevented by preincubation with a functional blocking antibody against human ICAM-1. These results suggest that LPLs released by activated platelets might enhance interactions of leukocytes with the endothelium through a G(i)-, NF-kappaB-, and possibly Rac-dependent mechanism, thus facilitating wound healing and inflammation processes.
Lee
Hsinyu
H
Department of Life Science and Institute of Zoology, National Taiwan University, Taipei, Taiwan 106, ROC. hsinyu@ntu.edu.tw
Lin
Chi Iou
CI
Liao
Jia-Jun
JJ
Lee
Yu-Wei
YW
Yang
Hsi Yuan
HY
Lee
Chung-Ying
CY
Hsu
Hsien-Yeh
HY
Wu
Hua Lin
HL
D036002:ADP Ribose Transferases / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D001905:Botulinum Toxins / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D020298:U937 Cells; D014471:Umbilical Veins / Q000166:cytology
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000975:Antioxidants; D001427:Bacterial Toxins; C488583:Clostridium difficile lethal toxin B; D008070:Lipopolysaccharides; D008246:Lysophospholipids; D016328:NF-kappa B; D009570:Nitriles; D011759:Pyrrolidines; D012333:RNA, Messenger; D013450:Sulfones; D013859:Thiocarbamates; C082161:lipopolysaccharide A; D018799:Intercellular Adhesion Molecule-1; C020972:pyrrolidine dithiocarbamic acid; C060506:sphingosine 1-phosphate; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D037342:Pertussis Toxin; D001905:Botulinum Toxins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D013110:Sphingosine