Objective: To investigate the mechanism whereby HIV-1 envelope glycoprotein
gp120 from four different isolates obtained in three different countries i
nduces proinflammatory mediator release from normal human basophils.
Methods: Histamine, cysteinyl leukotriene C-4 (LTC4) and interleukin 4 (IL-
4) release into the supernatant was measured in gp120-stimulated peripheral
blood basophils from HIV-1 and HIV-2 negative subjects.
Results: The HIV glycoprotein was a potent stimulus for release of these me
diators in basophils purified from donors negative for HIV-1 and HIV-2. The
re was also a correlation (r = 0.58; P < 0.01) between the maximum IL-4 rel
ease from basophils induced by gp120 and by anti-IgE. Basophils from which
IgE had been dissociated by brief exposure to lactic acid no longer release
d histamine in response to gp120 and anti-IgE. Anti-IgE specifically desens
itized basophils to a subsequent challenge with anti-IgE and gp120. Human m
onoclonal IgM carrying the V(H)3 domain, but not that carrying the V(H)6 do
main, inhibited gp120-induced secretion of histamine from basophils in a co
ncentration-dependent manner. Synthetic peptides identical to regions dista
nt from the N- and C-termini of gp120(MN) inhibited its activating capacity
. Conclusions: gp120 acts as a viral superantigen interacting with the V(H)
3 domain of IgE to induce the release of preformed and de novo synthesized
mediators from human cells carrying the Fc fragment Fc epsilon RI receptor.
(C) 2000 Lippincott Williams & Wilkins.