Anti-mu-opioid-receptor IgG antibodies are commonly present in serum from healthy blood donors: evidence for a role in apoptotic immune cell death.
We previously observed the presence of anti-human mu-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.
Macé
Gaëtane
G
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, 31059 Toulouse, France.
Jaume
Martial
M
Blanpied
Catherine
C
Stephan
Lionel
L
Coudert
Jérôme D
JD
Druet
Philippe
P
Dietrich
Gilles
G
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000502:physiology; D001782:Blood Donors; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006706:Homeostasis; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000097:blood* / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D019014:fas Receptor / Q000502:physiology
D001323:Autoantibodies; D007074:Immunoglobulin G; D017450:Receptors, Opioid, mu; D019014:fas Receptor