Endotoxin-induced migration of monocytes and PECAM-1 phosphorylation are abrogated by PAF receptor antagonists.
The trafficking of monocytes across the endothelial lining of the blood vessel increases in response to bacterial infection at sites of inflammation. However, the molecular events involved in the diapedesis of monocytes in response to endotoxin are not completely understood. Our studies revealed that signaling by lipopolysaccharide (LPS) in human umbilical vein endothelial cells (HUVEC) resulted in a threefold increase in the transendothelial migration of monocyte-like HL-60 cells and a sevenfold increase in the phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1). The transmigration induced by LPS was inhibited by an antibody to PECAM-1. Both the phosphorylation of PECAM-1 and transendothelial migration of monocytes were inhibited by a platelet-activating factor (PAF) receptor antagonist, indicating the autocrine effect of PAF in these events. Treatment of HUVEC with LPS caused a fourfold increase in PAF receptor mRNA expression that was completely blocked by the PAF receptor antagonist. We conclude that PAF, generated by HUVEC in response to LPS or gram-negative bacterial infection, acts in an autocrine manner, causing PECAM-1 phosphorylation and thus the transendothelial migration of monocytes.
Shen
Y
Y
Department of Biochemistry, Childrens Hospital Los Angeles, University of Southern California School of Medicine, Los Angeles, California 90033, USA.
Sultana
C
C
Arditi
M
M
Kim
K S
KS
Kalra
V K
VK
D001381:Azepines / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D005786:Gene Expression Regulation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008301:Maleimides / Q000494:pharmacology*; D008387:Marine Toxins; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D010080:Oxazoles / Q000494:pharmacology; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011726:Pyridinium Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014158:Transcription, Genetic / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology; D014471:Umbilical Veins
D001381:Azepines; D004731:Endotoxins; D007211:Indoles; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008301:Maleimides; D008387:Marine Toxins; D010080:Oxazoles; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C053321:CV 6209; C052518:WEB 2086; C059041:calyculin A; C070515:bisindolylmaleimide I