Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on July 1, 2005

Published online before print March 23, 2005
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow All Versions of this Article:
jlb.0105024v1
78/1/202    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schaffner, A.
Right arrow Articles by Schaer, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schaffner, A.
Right arrow Articles by Schaer, D. J.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0105024

Received for publication January 14, 2005.
Revised February 24, 2005.
Accepted for publication February 28, 2005.

Article

Regulated expression of platelet factor 4 in human monocytes--role of PARs as a quantitatively important monocyte activation pathway

Andreas Schaffner @, Petra Rhyn , Gabriela Schoedon , and Dominik J. Schaer

Research Unit Medizinische Klinik B, University of Zurich, Switzerland

@ To whom correspondence should be addressed. E-mail: klinsar{at}usz.unizh.ch.


  Abstract

Human mononuclear phagocytes have recently been shown to express constitutively and even more so, upon stimulation with bacteria, fungi, lipopolysaccharide (LPS), zymosan, or thrombin platelet basic protein (PBP). This CXC chemokine as well as platelet factor 4 (PF4), which is located genomically at a short distance from the PBP, were previously considered to be specific markers for the megakaryocyte cell lineage. Both chemokines have signaling and antimicrobial activity. In the present studies, transcriptional and expressional regulation of PF4 and related chemokines was studied in human monocytes. As shown by quantitative mRNA analysis, Western blots, radioimmunoprecipitation of cell extracts, and immunofluorescence and quantitatively with enzyme-linked immunosorbent assay, human monocytes express PF4 in the same order of magnitude as the known, regulated CXC chemokine interleukin (IL)-8. Expression of PF4 is up-regulated at the mRNA and protein level by thrombin and mediated by proteinase-activated receptors (PARs), resulting in a 32- to 128-fold higher mRNA level and leading to an up-to-sixfold increase of the peptide concentration in monocyte culture supernatants. Thrombin and the synthetic ligand of PAR-1 and PAR-2, SFLLRN, also induced comparable increases in the levels of mRNA for PBP, IL-8, regulated on activation, normal T expressed and secreted, monocyte chemoattractant protein-1, and macrophage-inflammatory protein-1{alpha} and increased synthesis of these chemokines as shown by immunofluorescence or a quantitative immunobead-based method. The induction of increased mRNA levels for all chemokines by SFLLRN was unsurpassed by LPS, zymosan, interferon-{gamma} (IFN-{gamma}), tumor necrosis factor {alpha} (TNF-{alpha}), and IL-1. Activation of monocytes through PARs represents an alternate activation mechanism, independent from IFN-{gamma}, TNF-{alpha}, or other signaling pathways.

Key Words: macrophages • thrombin • antimicrobial cationic peptides • {beta}-thromboglobulin • chemokines • receptors • proteinase-activated






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2005 by the Society for Leukocyte Biology.