Cytokine upregulation of surface antigens correlates to the priming of the neutrophil oxidative burst response.
BACKGROUND
Neutrophil activation is strongly related to organ dysfunction that occurs during systemic inflammatory responses. The aim of our study was to analyze the oxidative burst response in correlation to the up- and downregulation of N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP) receptors and the surface antigens CD11b, CD62L, and CD66b as potential surrogate markers of the degree of neutrophil priming for an increased oxidative burst response induced by proinflammatory cytokines.


METHODS
Blood was taken from healthy donors. Neutrophils were pretreated with cytokines (interleukin [IL]-1beta, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor [GM-CSF], and tumor necrosis factor alpha [TNFalpha]; 0.01-10 ng/ml) and stimulated with fMLP (100 nM) in vitro. Functional and phenotypical parameters were quantified flow cytometrically.


RESULTS
The oxidative burst response increased after priming with 0.1 ng/ml TNFalpha, 1 ng/ml GM-CSF, or 10 ng/ml IL-8. Upregulation of fMLP receptors, CD11b, and CD66b and downregulation of CD62L showed a close correlation to the oxidative burst response. Altered expression of these parameters partly reached significance at lower cytokine concentrations in comparison with the oxidative burst. IL-1beta and IL-6 had no effect.


CONCLUSIONS
Our results showed that the expression of phenotypical parameters closely correlates with functional parameters in human neutrophils. Thus an up- or downregulation of antigens such as CD11b or CD62L reflects cytokine-induced functional changes.
Wittmann
S
S
Department of Anesthesiology, University of Regensburg, 93042, Germany.
Rothe
G
G
Schmitz
G
G
Fröhlich
D
D
D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects* / Q000502:physiology; D012680:Sensitivity and Specificity; D015854:Up-Regulation
D000954:Antigens, Surface; D016207:Cytokines; D044042:Receptors, Formyl Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine