Activated platelets induce endothelial secretion of interleukin-8 in vitro via an interleukin-1-mediated event.
Migration of neutrophils through endothelial cells (EC) and induction of cytokine secretion are two well-documented events during the inflammatory reaction. The inflammatory, chemotactic cytokine interleukin-8 (IL-8) is secreted by EC in response to IL-1 stimulation. In this study, we show that platelets activated with either adenosine-5'-diphosphate or epinephrine induce IL-8 secretion by EC. This stimulatory activity was found to be associated with sedimented platelets after activation. Blockade of IL-1 receptors on EC with IL-1 receptor antagonist (IL-1Ra) decreased the stimulatory effect of whole activated platelet preparations by 59% (P < .05). Similarly, IL-1Ra pretreatment of EC reduced the stimulatory effect of sedimented activated platelets by 60% (P < .01). In addition, we treated human blood donors with 750 mg of oral aspirin, and evaluated the stimulatory effect of epinephrine-activated platelets on IL-8 secretion by EC. IL-8 synthesis after aspirin ingestion was inhibited by 90% (P < .01) as compared with the preaspirin stimulation. These observations show that activated platelets induce IL-8 secretion via membrane-associated IL-1 activity, and provide a novel relationship between coagulation and inflammation that could be relevant to several diseases.
Kaplanski
G
G
Department of Medicine, New England Medical Center Hospitals, Boston, MA 02111.
Porat
R
R
Aiura
K
K
Erban
J K
JK
Gelfand
J A
JA
Dinarello
C A
CA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism*; D007700:Kinetics; D015539:Platelet Activation; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology; D014471:Umbilical Veins
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016209:Interleukin-8; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D000244:Adenosine Diphosphate; D004837:Epinephrine