Blood, 1 November 2002, Vol. 100, No. 9, pp. 3261-3268
IMMUNOBIOLOGY
Anti-µ-opioid-receptor IgG antibodies are commonly present in
serum from healthy blood donors: evidence for a role in apoptotic
immune cell death
Gaëtane Macé,
Martial Jaume,
Catherine Blanpied,
Lionel Stephan,
Jérôme D. Coudert,
Philippe Druet, and
Gilles Dietrich
From Institut National de la Santé et de la
Recherche Médicale (INSERM) U563, Department of Oncogenesis and
Signaling in Haematopoietic Cells, Institut Claude de Préval, IFR
30, Hôpital Purpan, Faculté de Médecine Purpan,
Toulouse, France.
We previously observed the presence of anti-human
µ-opioid-receptor (anti-hMOR) autoantibodies in IgG pools prepared
from several thousand healthy blood donors. These autoantibodies
behaved agonistically because of their ability to bind to the first and third extracellular loops of the receptor. In this study, we found that
each healthy donor's serum contained anti-hMOR IgG autoantibodies with
a specific activity against both the first and the third extracellular
loops of the receptor. Because of the inability of IgG to cross the
blood-brain barrier, we investigated the effects of the expression of
anti-hMOR autoantibodies on immune cells. In analogy to studies of the
effects of morphine, we investigated the ability of antibodies to
sensitize splenocytes to Fas (CD95)-mediated apoptosis. We took
advantage of the high sequence homology between murine MOR and hMOR
extracellular loops to estimate the effect on murine splenocytes of
anti-hMOR antibodies raised by immunizing mice. Splenocytes from mice
injected with Chinese hamster ovary (CHO) cells expressing MOR were
sensitized to Fas-mediated apoptosis, whereas those from mice injected
with CHO cells or phosphate-buffered saline were not. Similar
sensitization to Fas-mediated apoptosis was observed in splenocytes
from mice undergoing passive transfer either with IgG from mice
previously immunized against CHO cells expressing MOR or with IgG
directed against the first and third extracellular loops of the
receptor. Together, our data show that anti-MOR autoantibodies are
commonly expressed in healthy humans and could participate in the
control of lymphocyte homeostasis by promoting Fas-mediated apoptosis.
