Nephrology Dialysis Transplantation, Vol 13, Issue 6 1412-1419, Copyright © 1998 by Oxford University Press
K Bauermeister, M Burger, N Almanasreh, H Knopf, R Schumann, P Schollmeyer and G Dobos
Background: Interleukin-8 and monocyte chemotactic
protein-1 (MCP-1) are major leukocyte chemoattractants during bacterial
peritonitis by recruiting neutrophils and monocytes/macrophages
respectively. Methods: Peritoneal macrophages (PM)
from 12 different CAPD patients with peritonitis were stimulated with
either 10 ng/ml LPS, 10 ng/ml IFN-&ggr; or LPS+IFN-&ggr;, and IL-8
and MCP-1 production was determined on protein and mRNA levels by using
ELISA technique and Northern blot analysis. To obtain information from two
different stages of activation, experiments were done with highly activated
PM directly after isolation and with cells after 10 days in culture, each
group being stimulated for 4 h. Unstimulated cells served as control.
Results: Immediately after isolation IL-8
mRNA-expression and synthesis was high and could be further increased by
LPS stimulation, whereas IFN-&ggr; treatment showed no significant
influence. The levels of MCP-1 were also initially high but could not be
further stimulated by LPS, whereas addition of IFN-&ggr; resulted in a
significant rise in MCP-1 synthesis. After 10 days in culture
LPS-stimulation of cells again revealed a significant increase in IL-8
protein synthesis, whereas IFN-&ggr; showed no effect. LPS anergy for
MCP-1 was still seen in PM after 10 days in culture, and IFN-&ggr;
treatment again induced a significant rise in MCP-1 synthesis. The overall
production of both chemokines was far higher on day 1 compared to day 10.
Conclusion: Our data show differences in
LPS/IFN-&ggr; regulation for IL-8 and MCP-1 in both highly activated
and in resting, mature peritoneal macrophages, suggesting distinct pathways
for these chemokines that may offer a means of control for the specific
recruitment of neutrophils and monocytes/macrophages in bacterial
peritonitis. Key words: CAPD; IFN-&ggr; IL-8; LPS;
MCP-1; peritoneal macrophages
ORIGINAL ARTICLES
Distinct regulation of IL-8 and MCP-1 by LPS and interferon-&ggr;-treated human peritoneal macrophages
Department of Nephrology, University Hospital Freiburg, Germany; Department of Immunology, Scripps Research Institute, La Jolla, USA; Max Planck Institute for Microbiology, Freiburg, Germany; Max Delbruck Centre for Molecular Medicine, Berlin, Germany; Corresponding author at: Im Bruehl 14, D-78086 Brigachtal, Geramny
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