A novel biological effect of platelet factor 4 (PF4): enhancement of LPS-induced tissue factor activity in monocytes.
In a previous study we have shown that granulocytes enhance lipopolysaccharide (LPS)-induced tissue factor (TF) activity in monocytes in a platelet-dependent reaction. The present investigation was undertaken to examine the role of a platelet activation product, platelet factor 4 (PF4), in LPS-induced TF activity in monocytes. Platelet lysate supernatant, purified PF4, and the COOH-terminal tridecapeptide of PF4, termed PF4(58-70), enhanced LPS-induced TF activity in monocytes of whole blood dose dependently. A monoclonal antibody against P-selectin eliminated the enhancing effect of PF4(58-70) on LPS-induced TF activity in monocytes, and PF4(58-70) was shown to act synergistically with tumor necrosis factor alpha (TNF-alpha). However, PF4(58-70) did not enhance TNF-alpha secretion in LPS-stimulated whole blood. The major effect of PF4(58-70) was granulocyte dependent. Our results suggest that PF4 might play an important role in LPS-stimulated monocyte TF activity of whole blood.
Engstad
C S
CS
Department of Biochemistry, Institute of Medical Biology, University of Tromsø, Norway.
Lia
K
K
Rekdal
O
O
Olsen
J O
JO
Osterud
B
B
D000595:Amino Acid Sequence; D000925:Anticoagulants / Q000008:administration & dosage; D001792:Blood Platelets / Q000378:metabolism; D002478:Cells, Cultured; D004357:Drug Synergism; D006098:Granulocytes / Q000502:physiology; D006493:Heparin / Q000008:administration & dosage; D006629:Hirudins / Q000008:administration & dosage; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D019007:P-Selectin / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage; D010978:Platelet Factor 4 / Q000008:administration & dosage*; D013925:Thromboplastin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
D000925:Anticoagulants; D006629:Hirudins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D019007:P-Selectin; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D010978:Platelet Factor 4; D006493:Heparin; D013925:Thromboplastin