Growth hormone inhibits apoptosis and up-regulates reactive oxygen intermediates production by human polymorphonuclear neutrophils.
BACKGROUND
Growth hormone (GH) regulates the immune and metabolic systems; however, the effects of GH on the functions and cell death of polymorphonuclear neutrophils (PMNs) are not well understood. Therefore, this study was designed to investigate the effects of GH on PMN apoptosis, reactive oxygen intermediates (ROI) production, CD16, and Fas expression. We also investigated the effects of GH on the functions of other circulating leukocytes (ie, monocytes and lymphocytes).


METHODS
Venous blood was collected from healthy volunteers. Whole blood was washed and pretreated with GH (0 or 100 ng/mL) for 3 hours and then cultured for 0, 4, or 12 hours. PMNs in washed whole blood were analyzed by flow cytometry for cell death, phorbol myristate acetate-stimulated ROI production, CD16, and Fas expression at each time point. Morphologic features also were assessed. PMN apoptosis was confirmed by chromatin staining and DNA gel electrophoresis.


RESULTS
GH inhibited PMN apoptosis at 12 hours of culture. GH enhanced ROI production by PMNs and monocytes throughout the 12-hour culture but had no effects on CD16 expression on PMNs. Furthermore, GH decreased Fas expression on PMNs at 4 hours of culture. However, there were no effects of GH on apoptosis of monocytes or lymphocytes for the duration of this experiment.


CONCLUSIONS
GH pretreatment down-regulates Fas expression on PMNs, inhibits apoptosis, and up-regulates ROI production. GH pretreatment also increases monocyte ROI production. Although activated PMNs have potentially harmful aspects, our results suggest that GH may improve host defense, mainly through enhancement of the PMN functional life span.
Matsuda
T
T
Department of Surgery, University of Tokyo, Japan.
Saito
H
H
Inoue
T
T
Fukatsu
K
K
Han
I
I
Furukawa
S
S
Ikeda
S
S
Muto
T
T
D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation; D005434:Flow Cytometry; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
D017382:Reactive Oxygen Species; D017452:Receptors, IgG; D019014:fas Receptor; D019382:Human Growth Hormone