Serum augments the generation of monocyte procoagulant stimulated by bacterial lipopolysaccharide or chemotactic fragments of C5.
Human serum augments the ability of bacterial lipopolysaccharide (endotoxin) or partially-purified C5-derived chemotactic fragments (C5-fr) to induce the monocyte procoagulant activity (PCA) in vitro. Both autologous and pooled sera induced PCA in the target cell population. Dose response curves revealed a detectable response in PCA with as little as 0.1% serum (v:v) in cell suspensions incubated for 4-6 hours before assay of PCA. Heat-inactivation experiments showed that enhancing activity of serum for both endotoxin and C5-fr induced-PCA could be destroyed by heating at 56 degrees C, with the greater part of the activity lost during the first 30 minutes of heating. The enhancing serums studied contained no endotoxin as measured by the Limulus amebocyte lysate assay and these serums failed to induce aggregation of neutrophils, a sensitive measure for the presence of complement-derived chemotactic fragments such as C5a. Serum without endotoxin or C5-fr also induced a variable increase in PCA and this inducing activity could also be abolished by heating, whereas the ability of endotoxin alone (10 micrograms/ml) to induce PCA was unaffected by similar heat-treatment. The procoagulant appeared to function as tissue factor in one-stage clotting assays using deficient substrate plasmas. Lymphocytes stimulated by serum and later washed failed to amplify monocyte tissue factor whereas lymphocytes exposed to endotoxin retained the ability to amplify monocyte tissue factor. These results suggest a role for serum in the modulation in vitro of monocyte procoagulant.
D000328:Adult; D000936:Antigen-Antibody Complex / Q000502:physiology; D001779:Blood Coagulation Factors / Q000096:biosynthesis*; D003182:Complement C5 / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D007136:Immunoglobulins / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D001779:Blood Coagulation Factors; D003182:Complement C5; D004731:Endotoxins; D007136:Immunoglobulins; D008070:Lipopolysaccharides