Recombinant human growth hormone (HuGH) and human prolactin (HuPRL), but not GH of bovine or porcine origin, prime human neutrophils for enhanced superoxide anion (O°) secretion. Since HuGH, but not GH of other species, effectively binds to the HuPRL receptor (HuPRL-R), we used a group of HuGH variants created by site-directed mutagenesis to identify the receptor on human neutrophils responsible for HuGH priming. A monoclonal antibody (MAb) directed against the HuPRL-R completely abrogated O2 secretion by neutrophils

The mechanism of CD4-mediated fusion via activated human immunodeficiency virus type 1 (HIV-1) gp4l and the biological significance of soluble CD4 (sCD4)-induced shedding of gpl20 are poorly understood. The purpose of these investigations was to determine whether shedding of gpl20 led to fusion activation or inactivation. BJAB cells (TF228.1.16) stably expressing HIV-1 envelope glycoproteins (the gpl2O-gp4l complex) were used to examine the effects of pH and temperature on sCD4-induced shedding of gpl20 and on cell-to-cell fusion (syncytium formation) with CD4+ SupTi cells. sCD4-induced shedding of gpl20 was maximal at pH 4.5 to 5.5 and did not occur at pH 8.5. At physiologic pH, sCD4-induced shedding of gpl20 occurred at 22, 37, and 40°C but neither at 16 nor 4°C. In contrast, syncytia formed at pH 8.5 (maximally at pH 7.5) but not at pH 4.5 to 5.5. At pH 7.5, syncytia formed at 37 and 40°C but not at 22, 16, or 4°C. Preincubation of cocultures of TF228.1.16 and SupTi cells at 4, 16, or 22°C before the shift to 37°C resulted in similar,

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 02-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-y) or 250 ng of growth hormone (GH) per ml. This priming is specific, because neutralizing monoclonal antibodies against either IFN-y or GH completely abrogate the enhanced 02-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-y (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 02 secretion by IFN-y (25 U/ml). Although PMN from aged rats do not respond to the lower doses of either IFN-y or GH, the combination of both reagents totally restores the ability of PMN to secrete 02 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.

No abstract

No abstract