TY - JOUR
T1 - Reduction in superoxide anion secretion and bactericidal activity of neutrophils from aged rats
T2 - Reversal by the combination of gamma interferon and growth hormone
AU - Fu, Y. K.
AU - Arkins, S.
AU - Yong Ming Li, Ming Li
AU - Dantzer, R.
AU - Kelley, K. W.
PY - 1994
Y1 - 1994
N2 - Polymorphonuclear neutrophils (PMN) from bone marrow of 24-month-old rats kill Escherichia coli less efficiently than PMN from 3-month-old rats. Secretion of O2- and killing of E. coli by PMN from both young and old rats can be significantly augmented by preincubation with either 250 U of gamma interferon (IFN-γ) or 250 ng of growth hormone (GH) per ml. This priming is specific, because neutralizing monoclonal antibodies against either IFN-γ or GH completely abrogate the enhanced O2- secretion by PMN from young rats. However, in contrast to PMN from young rats, PMN from aged rats are not primed to kill E. coli by 10-fold-lower concentrations of either IFN-γ (25 U/ml) or GH (25 ng/ml). To explore the mechanism for the reduction in bacterial killing by PMN from old rats, a syngeneic GH-secreting pituitary cell line (GH3) was implanted in vivo. PMN from GH3-treated aged rats, but not control aged rats, could now be primed in vitro for O2- secretion by IFN-γ (25 U/ml). Although PMN from aged rats do not respond to the lower doses of either IFN-γ or GH, the combination of both reagents totally restores the ability of PMN to secrete O2- and to kill E. coli. This synergistic priming is observed with PMN from aged rats, but not with those from young rats, and can be detected when both reagents are added simultaneously or when they are added in either sequence. Furthermore, addition of a monoclonal antibody against either IFN-γ or GH abrogates the synergism of these two molecules. Collectively, these data identify an important alteration in myeloid cells from aged rodents by showing that their PMN are intrinsically unable to respond to low concentrations of IFN-γ by secreting O2- and killing bacteria. The results also define a previously unrecognized synergism in PMN from aged animals by showing that GH synergizes with IFN-γ both in vivo and in vitro to restore these suppressed responses.
AB - Polymorphonuclear neutrophils (PMN) from bone marrow of 24-month-old rats kill Escherichia coli less efficiently than PMN from 3-month-old rats. Secretion of O2- and killing of E. coli by PMN from both young and old rats can be significantly augmented by preincubation with either 250 U of gamma interferon (IFN-γ) or 250 ng of growth hormone (GH) per ml. This priming is specific, because neutralizing monoclonal antibodies against either IFN-γ or GH completely abrogate the enhanced O2- secretion by PMN from young rats. However, in contrast to PMN from young rats, PMN from aged rats are not primed to kill E. coli by 10-fold-lower concentrations of either IFN-γ (25 U/ml) or GH (25 ng/ml). To explore the mechanism for the reduction in bacterial killing by PMN from old rats, a syngeneic GH-secreting pituitary cell line (GH3) was implanted in vivo. PMN from GH3-treated aged rats, but not control aged rats, could now be primed in vitro for O2- secretion by IFN-γ (25 U/ml). Although PMN from aged rats do not respond to the lower doses of either IFN-γ or GH, the combination of both reagents totally restores the ability of PMN to secrete O2- and to kill E. coli. This synergistic priming is observed with PMN from aged rats, but not with those from young rats, and can be detected when both reagents are added simultaneously or when they are added in either sequence. Furthermore, addition of a monoclonal antibody against either IFN-γ or GH abrogates the synergism of these two molecules. Collectively, these data identify an important alteration in myeloid cells from aged rodents by showing that their PMN are intrinsically unable to respond to low concentrations of IFN-γ by secreting O2- and killing bacteria. The results also define a previously unrecognized synergism in PMN from aged animals by showing that GH synergizes with IFN-γ both in vivo and in vitro to restore these suppressed responses.
UR - http://www.scopus.com/inward/record.url?scp=0027976232&partnerID=8YFLogxK
M3 - Article
C2 - 8262614
AN - SCOPUS:0027976232
SN - 0019-9567
VL - 62
SP - 1
EP - 8
JO - Infection and Immunity
JF - Infection and Immunity
IS - 1
ER -