Cytokine Profile Associated with Selective Removal of Natural Anti-αGal Antibodies in a Sepsis Model in Gal-KO Mice

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Magdiel Pérez-Cruz^1#, Daniel Bello-Gil^1#, Cristina Costa¹, and Rafael Mañez^1,2*

¹Bellvitge Biomedical Research Institute (IDIBELL), Gran Via de l’Hospitalet 199, 08908-Hospitalet de Llobregat, Spain

²Bellvitge University Hospital, Feixa Llarga s/n, 08907-Hospitalet de Llobregat, Spain; E-mail: rmanez@bellvitgehospital.cat

^# These authors contributed equally to this work.

^* To whom correspondence should be addressed.

Received July 4, 2016; Revision received September 5, 2016

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Selective depletion of natural anti-Galα1-3Galβ1-4GlcNAc (so-called anti-αGal) antibodies is achieved in α1,3-galactosyltransferase knockout (Gal-KO) mice by administration of the soluble glycoconjugate of αGal GAS914. This molecule removed up to 90% of natural circulating anti-αGal antibodies without causing unspecific production of cytokines in wild-type (CBA) and Gal-KO mice. However, the removal of anti-αGal antibodies in Gal-KO mice with GAS914 in the context of sepsis after cecal ligation and puncture (CLP) was associated with a significant increase in the production of leptin, CXLC1, CXLC13, and TIMP-1 cytokines compared to vehicle (PBS)-treated controls. Despite the current lack of understanding of the underlying mechanism, our data suggest a putative role of natural anti-αGal antibodies in the regulation of some cytokines during sepsis.

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KEY WORDS: natural antibodies, anti-αGal, glycoconjugates, GAS914, cytokines, inflammation, sepsis

DOI: 10.1134/S0006297917020122

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