Impaired neutrophils in children with the typical form of hemolytic uremic syndrome.
Experimental and clinical evidence suggest that activated neutrophils (PMN) could contribute to endothelial damage in Hemolytic Uremic Syndrome (D+HUS). Additionally, while PMN-activating cytokines and PMN-derived products have been found in D+HUS sera, we have demonstrated phenotypic alterations in D+HUS PMN compatible with a deactivation state. Here, we investigated whether D+HUS PMN were actually hyporesponsive, and explored some of the mechanisms probably involved in their derangement. Twenty-two D+HUS children were bled in the acute period, and blood samples from healthy, acute uremic and neutrophilic children were obtained as controls. We evaluated degranulation markers in response to cytokines, intracellular granule content, and reactive oxygen species (ROS) generation in circulating D+HUS and control PMN. The influence of D+HUS-derived plasma and the direct effects of Stx in vitro were evaluated on healthy donors' PMN. We found that D+HUS PMN presented reduced degranulatory capacity in response to cytokines and intracellular granule content, and decreased ROS generation. D+HUS plasma or Stx did not affect the phenotype and function of healthy donors' PMN. These results suggest that upon hospitalization D+HUS PMN are functionally impaired and show features of previous degranulation, indicating a preceding process of activation with release of ROS and proteases involved in endothelial damage.
Fernández
Gabriela C
GC
Department of Immunology, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina. gfernandez@hematologia.anm.edu.ar
Gómez
Sonia A
SA
Rubel
Carolina J
CJ
Bentancor
Leticia V
LV
Barrionuevo
Paula
P
Alduncín
Marta
M
Grimoldi
Irene
I
Exeni
Ramón
R
Isturiz
Martín A
MA
Palermo
Marina S
MS
D015550:Cell Degranulation / Q000276:immunology; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010447:Peptide Hydrolases / Q000032:analysis; D017382:Reactive Oxygen Species / Q000032:analysis
D017382:Reactive Oxygen Species; D010447:Peptide Hydrolases