Abstract
Human mesothelial cells synthesize plasminogen activator inhibitor (PAI) 1 in inflamed peritoneal tissue. The role of tumour necrosis factor (TNF) in the mediation of this response was studied. Postoperative peritoneal drain fluid contained both TNF and PAI-1. Peak levels of TNF at 4 h (median 271 pg/ml) preceded a rise in PAI-1 concentration, which peaked at 18 h (median 943·1 ng/ml). Thus TNF may mediate increased PAI-1 release in inflamed peritoneum. TNF significantly increased the mean(s.e.m.) release of PAI-1 by human peritoneal mesothelial cells in vitro at 4 h (control 1·84(0·17) ng/μg versus TNF 2·37(0·17) ng/μg, P0·05), 6 h (2·53(0·09) versus 3·88(0·46) ng/μg, P<0·05), 18 h (0·50(0·02) versus 1·04(0·11) ng/μg, P<0·05) and 24 h (0·87(0·05) versus 1·35(0·11)ng/μg, P<0·05). TNF may be an important mediator of PAI-1 production by human mesothelial cells during peritoneal inflammation.
Contributor Information
Dr S A Whawell, Department of Surgery, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
D M Scott-Coombes, Department of Surgery, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
M N Vipond, Department of Surgery, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
S J Tebbutt, Department of Surgery, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
J N Thompson, Department of Surgery, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
References
- 1. Thompson JN, Paterson-Brown S, Harbourne T, Whawell SA, Kalodiki E, Dudley HAF. Reduced human peritoneal plasminogen activating activity: a possible mechanism of adhesion formation. Br J Surg 1989; 76: 382–4. [DOI] [PubMed] [Google Scholar]
- 2. Vipond MN, Whawell SA, Thompson JN, Dudley HAF. Peritoneal fibrinolytic activity and intra-abdominal adhesions. Lancet 1990; ii: 1120–2. [DOI] [PubMed] [Google Scholar]
- 3. Whawell SA, Wang Y, Fleming KA, Thompson EM, Thompson JN. Localisation of plasminogen activator inhibitor-1 production in inflamed appendix by in situ mRNA hybridisation. J Pathol 1993; 169: 67–71. [DOI] [PubMed] [Google Scholar]
- 4. Emeiss JJ, Kooistra T. Interleukin-1 and lipopolysaccharide induce an inhibitor of tissue-type plasminogen activator in vivo and in cultured endothelial cells. J Exp Med 1986; 163: 1260–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Hanss M, Collen D. Secretion of tissue type PA and PAI by cultured human endothelial cells: modulation by thrombin, endotoxin and histamine. J Lab Clin Med 1987; 109: 97–107. [PubMed] [Google Scholar]
- 6. Van Hinsbergh VWM, Kooistra T, Van den Berg EA, Princen HMG, Fiers W, Emeiss JJ. Tumour necrosis factor increases the production of plasminogen activator inhibitor in human endothelial cells in vitro and in rats. in vivo. Blood 1988; 72: 1467–73. [PubMed] [Google Scholar]
- 7. Schleef RR, Bevilacqua MP, Saudey M, Gimbrane MA, Loskutoff DJ. Cytokine activation of vascular endothelium. J Biol Chem 1988; 263: 5797–803. [PubMed] [Google Scholar]
- 8. Van den Berg EA, Spengers ED, Jaye M, Burgess W, Maciag T, Van Hinsbergh VWM. Regulation of plasminogen activator inhibitor-1 mRNA in human endothelial cells. Thromb Haemost 1988; 60: 63–7. [PubMed] [Google Scholar]
- 9. La Rocca PJ, Rheinwald JG. Anchorage independent growth of normal human mesothelial cells. In Vitro Cell Dev Biol 1985; 21: 67–72. [DOI] [PubMed] [Google Scholar]
- 10. Connell ND, Rheinwald JG. Regulation of the cytoskeleton in mesothelial cells: reversible loss of keratin and increase in vimentin during rapid growth in culture. Cell 1983; 34: 245–53. [DOI] [PubMed] [Google Scholar]
- 11. Wu YJ, Parker LM, Binder WE et al. The mesothelial keratins: a new family of cytoskeletal proteins identified in cultured mesothelial cells and nonkeratinizing epithelia. Cell 1982; 31: 693–703. [DOI] [PubMed] [Google Scholar]
- 12. Bradford MM. A rapid and sensitive method for the quantitatia of microgram quantities of protein utilising the principle of protein-dye binding. Anal Biochem 1976; 72: 248–54. [DOI] [PubMed] [Google Scholar]
- 13. Van Deuren M, Dofferhoff ASM, Van der Meer JWM. Cytokines and the response to infection. J Pathol 1992; 168: 349–56. [DOI] [PubMed] [Google Scholar]
- 14. Van Hinsbergh VWM, Baner KA, Kooistra T et al. Progress of fibrinolysis during tumour necrosis factor infusions in humans. Blood 1990; 76: 2284–9. [PubMed] [Google Scholar]
- 15. Van der Poll T, Levi M, Buller HR et al. Fibrinolytic response to tumour necrosis factor in healthy subjects. J Exp Med 1991; 174: 729–32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Nedwin GE, Svedersky LP, Bringman TS, Palladino MA, Goeddel DV. Effect of interleukin 2, interferon gamma and mitogens on the production of tumour necrosis factors α and β. J Immunol 1985; 135: 2492–7. [PubMed] [Google Scholar]
- 17. Waage A, Halstensen A, Shalaby R, Brandtzaeg P, Kierulf P, Espevik T. Local production of tumour necrosis factor α, interleukin 1 and interleukin 6 in meningococcal meningitis. J Exp Med 1989; 170: 1859–67. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Remick DG, Stricter RM, Lynch JP, Nguyen D, Eskandari M, Kunkel SL. In vivo dynamics of murine tumour necrosis factor gene expression. Lab Invest 1989; 60: 766–71. [PubMed] [Google Scholar]
- 19. Cicila GT, O'Connell TM, Hahn WC, Rheinwald JG. Cloned cDNA sequence for the human mesothelial protein ‘mesosecrin’ discloses its identity as a plasminogen activator inhibitor (PAI-1) and a recent evolutionary change in transcript processing. J Cell Sci 1989; 94: 1–10. [DOI] [PubMed] [Google Scholar]
- 20. Van Hinsbergh VWM, Kooistra T, Schaffer MA, Van Bockel JM, Van Muijen GMP. Characterisation and fibrinolytic properties of human omental tissue mesothelial cells. Comparison with endothelial cells. Blood 1990; 75: 1490–7. [PubMed] [Google Scholar]