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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Immunol
2017 ; 8
(ä): 188
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Molluskan Hemocyanins Activate the Classical Pathway of the Human Complement
System through Natural Antibodies
#MMPMID28286504
Pizarro-Bauerle J
; Maldonado I
; Sosoniuk-Roche E
; Vallejos G
; López MN
; Salazar-Onfray F
; Aguilar-Guzmán L
; Valck C
; Ferreira A
; Becker MI
Front Immunol
2017[]; 8
(ä): 188
PMID28286504
show ga
Molluskan hemocyanins are enormous oxygen-carrier glycoproteins that show
remarkable immunostimulatory properties when inoculated in mammals, such as the
generation of high levels of antibodies, a strong cellular reaction, and
generation of non-specific antitumor immune responses in some types of cancer,
particularly for superficial bladder cancer. These proteins have the ability to
bias the immune response toward a T(h)1 phenotype. However, despite all their
current uses with beneficial clinical outcomes, a clear mechanism explaining
these properties is not available. Taking into account reports of natural
antibodies against the hemocyanin of the gastropod Megathura crenulata [keyhole
limpet hemocyanin (KLH)] in humans as well as other vertebrate species, we report
here for the first time, the presence, in sera from unimmunized healthy donors,
of antibodies recognizing, in addition to KLH, two other hemocyanins from
gastropods with documented immunomodulatory capacities: Fisurella latimarginata
hemocyanin (FLH) and Concholepas concholepas hemocyanin (CCH). Through an ELISA
screening, we found IgM and IgG antibodies reactive with these hemocyanins. When
the capacity of these antibodies to bind deglycosylated hemocyanins was studied,
no decreased interaction was detected. Moreover, in the case of FLH,
deglycosylation increased antibody binding. We evaluated through an in vitro
complement deposition assay whether these antibodies activated the classical
pathway of the human complement system. The results showed that all three
hemocyanins and their deglycosylated counterparts elicited this activation,
mediated by C1 binding to immunoglobulins. Thus, this work contributes to the
understanding on how the complement system could participate in the
immunostimulatory properties of hemocyanins, through natural,
complement-activating antibodies reacting with these proteins. Although a role
for carbohydrates cannot be completely ruled out, in our experimental setting,
glycosylation status had a limited effect. Finally, our data open possibilities
for further studies leading to the design of improved hemocyanin-based research
tools for diagnosis and immunotherapy.