title: Cytokine mRNA expression in human platelets and a megakaryocytic cell line and cytokine modulation of platelet function.
abstract: Platelet formation and function are regulated, in vivo, to varying degrees by cytokines in the micro-environment. While white blood cells are the major source of cytokines within the cardiovascular system, the question addressed in this study was whether platelets and the platelet precursor, the megakaryocyte, may also serve as a source of cytokines. Cytokines produced by or carried within platelets could be released at sites of vascular injury and participate in wound healing. Platelets and a human megakaryocyte-like cell line, HU3, were found to express message for interleukin 7 (IL-7), stem cell factor (SCF), transforming growth factor beta (TGF-beta), cMpl, the IgE receptor subunits Fc epsilon RI alpha gamma and the transcription factor, NF-E2. Other cytokines expressed in HU3 cells but not in platelets included IL-1 beta, IL-6, IL-10, IL-13, TNF-alpha and the FC epsilon RI beta subunit. The HU3 cell line seemed to be further along the maturation/differentiation pathway to platelet formation than a second blood derived bipotential cell line, MB02. The MB02 cell line did not express IL-6, IL-10, SCF, TNF-omega nor cMpl. Furthermore, culturing the HU3 cells in TPO appeared to repress expression of Fc epsilon RI beta directing the cell closer to the platelet phenotype. In light of the presence of cytokine expression in platelets/megakaryocytes, agonist-induced platelet aggregation was measured in the presence of added cytokines as a means to evaluate potential cytokine modulation of platelet function. Collagen-induced aggregations were significantly enhanced by IL-6, SCF and TPO. Other cytokines tested significantly stimulated the thrombin receptor activating peptide, SFLLRNP-, U46619- and ADP-induced platelet aggregations with TPO being the most consistent activator. It is possible that cytokines released from platelets act in concert with cytokines released from other cellular sources to modulate haemostasis and thrombosis differentially depending upon the site of injury.
authors.affiliation: Department of Biochemistry/IMS, Allegheny University of the Health Sciences, Philadelphia, PA 19102, USA.
authors.forename: G
authors.initials: G
authors.lastname: Soslau
authors.forename: D A
authors.initials: DA
authors.lastname: Morgan
authors.forename: J S
authors.initials: JS
authors.lastname: Jaffe
authors.forename: I
authors.initials: I
authors.lastname: Brodsky
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D003094:Collagen / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics* / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008533:Megakaryocytes / Q000276:immunology* / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D017455:Receptors, IgE / Q000235:genetics
chemical_list: D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D017455:Receptors, IgE; D003094:Collagen