DIRECT INDUCTION OF TISSUE FACTOR SYNTHESIS BY ENDOTOXIN IN HUMAN MACROPHAGES FROM DIVERSE ANATOMICAL SITES
- 1 January 1983
- journal article
- research article
- Vol. 50 (4) , 529-535
Abstract
On exposure to endotoxin and other stimuli, human peripheral blood mononuclear cells generate a potent procoagulant activity (PCA), identified as tissue factor. Although it is now recognized that the monocytes are the source of PCA, the question whether these cells per se are capable of procoagulant response to endotoxin or require lymphocyte collaboration remains unsettled. The capacity of highly purified human macrophages from diverse anatomical sites to generate PCA following endotoxin stimulation was investigated. Purified (> 99%) monocyte-derived macrophages were obtained by prolonged (3-10 days) in vitro culture of adherent monocytes using medium supplemented with 50% human serum. Purified (> 95%) peritoneal and milk macrophages were isolated by adherence to plastic. PCA was measured before and after incubation (4 h at 37.degree.) with endotoxin (Salmonella enteritidis LPS [lipopolysaccharide], W or Escherichia coli O111:B4LPS, W, 1 .mu.g/ml final concentration) using 1-stage clotting assay and or a 2-stage amidolytic assay. Monocyte-derived macrophages had low baseline PCA (14-19 U/105 cells) but, on exposure to endotoxin, displayed an 8-fold increase in PCA over control. Peritoneal and milk macrophages expressed very low baseline activity (1-5 U/105 cells). The latter increased 15-20 times over control following endotoxin stimulation. PCA was identified as tissue factor by biological and immunological criteria. Its generation was completely abolished by cycloheximide. In the human mononuclear phagocyte series the capacity to produce PCA is not restricted to circulating monocytes but is also expressed by macrophages obtained from diverse anatomical sites. These macrophages appear to be autonomous in their procoagulant response to endotoxin.This publication has 25 references indexed in Scilit:
- Synthesis of thromboplastin by U-937 cellsBritish Journal of Haematology, 1982
- Immune complex-induced human monocyte procoagulant activity. I. a rapid unidirectional lymphocyte-instructed pathway.The Journal of Experimental Medicine, 1981
- Augmentation of tumoricidal activity of human monocytes and macrophages by lymphokinesInternational Journal of Cancer, 1980
- Cancer cell procoagulant activity: Evaluation by an amidolytic assayThrombosis Research, 1980
- Lymphocyte cooperation is required for amplification of macrophage procoagulant activity.The Journal of Experimental Medicine, 1980
- The separation, long-term cultivation, and maturation of the human monocyte.The Journal of Experimental Medicine, 1977
- Counts and characteristics of macrophage precursors in human peripheral bloodCellular Immunology, 1975
- POSSIBLE PATHOGENIC ROLE OF ENDOTOXIN IN REYE'S SYNDROMEThe Lancet, 1975
- Alpha Thalassaemia in Adults with Sickle‐Cell TraitBritish Journal of Haematology, 1975
- EFFECT OF NORMAL AND ACTIVATED HUMAN MACROPHAGES ON TOXOPLASMA GONDII The Journal of Experimental Medicine, 1974