Neutrophil-mediated endothelial injury in haemolytic uraemic syndrome.
Neutrophil leucocytosis is associated with a poor outcome in the haemolytic uraemic syndrome (HUS). This study tested the hypothesis that neutrophils from HUS patients are activated and through release of their intracellular contents damage endothelium. The proportion of neutrophils adhering to endothelium in culture was twice as high for HUS patients' neutrophils as for control neutrophils (n = 12). In addition, these neutrophils induced endothelial injury, assessed morphologically by degradation of endothelial cell fibronectin. In an attempt to inhibit neutrophil adhesion and subsequent endothelial damage the hyperadhesive neutrophils from HUS patients were incubated with a CD18 antibody directed against the common beta chain of the leucocyte integrin molecules. The CD18 antibody was able to abrogate endothelial damage in four of the ten subjects studied. These observations suggest that the neutrophil is of prime pathophysiological importance in HUS, and that methods aimed at reducing neutrophil adhesion and neutrophil-mediated endothelial damage are likely to be beneficial.
Forsyth
K D
KD
Department of Immunology, University of London.
Simpson
A C
AC
Fitzpatrick
M M
MM
Barratt
T M
TM
Levinsky
R J
RJ
D000208:Acute Disease; D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002448:Cell Adhesion; D002675:Child, Preschool; D003967:Diarrhea / Q000209:etiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000150:complications / Q000378:metabolism; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*
D000911:Antibodies, Monoclonal; D005353:Fibronectins