Abstract
Vascular endothelial damage is a major component of the physiological derangement seen in septicaemia. The sulphated glycosaminoglycans (GAGS) are thought to be involved in regulating endothelial permeability, thromboresistance and leucocyte traffic across the blood vessel wall. Modulation of GAG metabolism may therefore be important in causing the capillary leak and disseminated intravascular thrombosis often seen in bacterial sepsis.
We have previously shown that the cytokines IL1 and TNF modulate glycosaminoglycan metabolism, resulting in a reduction of heparan and dermatan sulphate from the cell surface of cultured human umbilical vein endothelial cell cultures (HUVEC).
In the present study we have investigated the correlation between neutrophil activation and endothelial cell damage. To perform these experiments we have developed an endothelial model of surface injury using a cytochemical technique to visualise both endothelial GAGS and cellular fibronectin.
Results: We have demonstrated that the release of neutrophil proteases and neutrophil heparatinase are determined by the degree of both neutrophil and endothelial activation. When unstimulated neutrophils were added to HUVEC prestimulated with endotoxin, GAGS alone were degraded from the endothelial cell surface. However, when the formyl tripeptide, fMLP, was included in the incubation, we also observed extensive destruction of the protease sensitive fibronectin network. When endotoxin and fMLP were added simultaneously with the neutrophils there was minimal endothelial damage.
Conclusion: These results indicate that both neutrophil and endothelial activation is necessary to cause the breakdown of endothelial GAGS and fibronectin. These results may be important in understanding the mechanisms of neutrophil induced endothelial damage in inflammation.
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Klein, N., Finn, A. & Heyderman, R. DEGRADATION OF ENDOTHELIAL SURFACE GLYCOSAMINOGLYCANS AND FIBRONECTIN FOLLOWING TREATMENT WITH ENDOTOXIN AND NEUTROPHILS. Pediatr Res 32, 624 (1992). https://doi.org/10.1203/00006450-199211000-00114
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DOI: https://doi.org/10.1203/00006450-199211000-00114