Idiopathic neutropenia of childhood is associated with Fas/FasL expression.
Idiopathic neutropenia (IN) in children is characterized by decreased neutrophil counts (<1500/microl), can be acute or chronic (greater than 6 months duration). The pathophysiology is not well understood; therefore, potential mechanisms of pediatric IN were investigated. An increase in Fas transcripts in neutrophils of IN patients compared to age-matched healthy control (HC) neutrophils was observed (p<0.005). Increased expression of Fas protein was found in IN neutrophils, while Fas surface expression on other immune cells was similar. Plasma from acute IN patients had higher protein levels of soluble FasL than chronic IN patients. When HC neutrophils were incubated in plasma from IN patients, greater rates of apoptosis were observed. Biochemical studies suggest the apoptotic factor(s) in plasma is heat-sensitive, non-IgG, and 12-50 kD protein. Addition of anti-sFasL blocking antibodies to patient plasma caused a statistically significant decrease in neutrophil apoptosis. These studies show that the Fas/FasL pathway could be associated with neutrophil apoptosis in childhood IN.
Nadeau
Kari C
KC
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA. knadeau@stanford.edu
Callejas
Angel
A
Wong
Wendy B
WB
Joh
Jae Won
JW
Cohen
Harvey J
HJ
Jeng
Michael R
MR
D017209:Apoptosis / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology; D053222:Fas Ligand Protein / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D009503:Neutropenia / Q000097:blood / Q000276:immunology* / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics
D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007074:Immunoglobulin G; D019014:fas Receptor