C5a-induced expression of P-selectin in endothelial cells.
Human umbilical vein endothelial cells have recently been shown to respond to C5a with increases in intracellular Ca2+, production of D-myo-inositol 1,4,5-triphosphate and superoxide anion generation. In the current studies, C5a had been found to cause in a time- and dose-dependent manner rapid expression of endothelial P-selectin, secretion of von Willebrand factor, and adhesiveness for human neutrophils. The effects of C5a in P-selectin expression and adhesiveness of neutrophils were similar to the effects of histamine and thrombin on endothelial cells. The adhesiveness of C5a-stimulated endothelium for neutrophils was blocked by anti-P-selectin, but not by antibodies to intercellular adhesion molecule 1, E-selectin, or CD18. A cell-based ELISA technique has confirmed upregulation of P-selectin in endothelial cells exposed to C5a. Binding of C5a to endothelial cells has been demonstrated, with molecules bound being approximately 10% of those binding to neutrophils. By a reverse transcriptase-PCR technique, endothelial cells have been shown to contain mRNA for the C5a receptor. These data suggest that C5a may be an important inflammatory mediator for the early adhesive interactions between neutrophils and endothelial cells in the acute inflammatory response.
Foreman
K E
KE
Parke-Davis Research Division of Warner-Lambert Company, Ann Arbor, Michigan 48105.
Vaporciyan
A A
AA
Bonish
B K
BK
Jones
M L
ML
Johnson
K J
KJ
Glovsky
M M
MM
Eddy
S M
SM
Ward
P A
PA
D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D015936:Complement C5a / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000502:physiology; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D014471:Umbilical Veins; D014841:von Willebrand Factor / Q000032:analysis / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D015936:Complement C5a; D006632:Histamine