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Effect of human recombinant cytokines on the induction of macrophage
procoagulant activity
I Schwager and TW Jungi
Institute of Veterinary Virology, University of Berne, Switzerland.
A panel of human recombinant cytokines was tested for induction of
procoagulant activity (PCA) in human monocyte-derived macrophages.
Nonadherent culture conditions were used, and PCA was determined with whole
cells rather than cell lysates. It was assured by Limulus amebocyte lysate
assay that tested cytokines displayed low levels of endotoxin activity
within the range of biologic activity. Additional evidence to rule out an
endotoxin effect was provided by heat- inactivation experiments.
Interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta), and tumor
necrosis factor-alpha (TNF-alpha) were strong macrophage PCA inducers. The
low level of PCA induced by IL-2, granulocyte-macrophage colony-stimulating
factor (GM-CSF), M-CSF, IL-4, IL-6, IL-10, and IFN-alpha could not be
distinguished from that induced by traces of endotoxin contaminating the
preparations. Transforming growth factor-beta decreased constitutively
expressed PCA within 24 hours of exposure. PCA induced by IFN-gamma, IL-1
beta, and TNF-alpha depended largely on tissue factor expression, as
evidenced by experiments with factor X-deficient plasma and antitissue
factor antibodies. In macrophages subcultured in adherence, IL-1 beta was a
strong PCA inducer, whereas IFN-gamma and TNF-alpha promoted little PCA
increase. This observation and different kinetics of PCA induction
suggested that mechanisms of PCA induction are distinct for the three
cytokines. Thus, we showed that well-characterized cytokines critically
involved in the promotion of cell-mediated antimicrobial
defense/delayed-type hypersensitivity and considered for clinical
application promote local fibrin deposition by a direct effect on
macrophages.
Volume 83,
Issue 1,
pp. 152-160,
01/01/1994
Copyright © 1994 by The American Society of Hematology
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