Regulation of monocyte procoagulant by chemoattractants
RL Janco and PJ Morris
Various n-formylated peptides function as receptor-specific
chemoattractants for both granulocytes and monocytes. Because these agents
are important tools in the study of leukocyte function in vitro, we chose
to examine their effects on leukocyte procoagulant activity. The synthetic
chemotactic peptide N-formyl-methionyl-leucyl phenylalanine (FMLP) induces
a fourfold increase in procoagulant activity (PCA) in cultured human
monocytes at an optimal dose of 5 X 10(-9) mol/L, whereas higher doses
inhibit PCA response. Although nonadherent lymphocytes are not absolutely
required for PCA expression, their presence significantly amplifies
monocyte PCA. Irradiation of nonadherent lymphocytes before mixing them
with FMLP and adherent cells abolishes their ability to amplify PCA.
Kinetic studies demonstrate an increase in optimal dose FMLP-stimulated PCA
over time whereas high- dose inhibition of PCA generation occurs at various
incubation times. Cell viability is unaffected by inhibitory concentrations
of FMLP. Supernates from high-dose FMLP-stimulated cells fail to inhibit
later expression of PCA by cells exposed to endotoxin. The cellular
procoagulant remains cell-bound and exhibits characteristics of
thromboplastin (tissue factor), including inhibition by concanavalin A and
phospholipase C as well as the ability to shorten the clotting times of
factor VIII but not factor VII-deficient substrate plasmas. These results
suggest a complex system of lymphoid cell regulation of procoagulant
generation by monocytes exposed to various chemotactic peptides in vitro.
Volume 65,
Issue 3,
pp. 545-552,
03/01/1985
Copyright © 1985 by The American Society of Hematology
