Reduction of asialo pathway gangliosides in Escherichia coli-activated peritoneal macrophages from endotoxin hyporesponsive mice

Abstract

Sialidase-sensitive gangliosides are reduced in endotoxin-activated macrophages from C3H/HeJ mice. Ganglioside variation in mice has been linked to the H-2 complex. The H-2 gene locus is the major histocompatibility complex of the mouse which encodes for major cell surface antigens as well as immune response genes (the Ir genes). To determine whether the ganglioside alteration is a direct pleotropic influence of the Lps defect or whether there is an indirect influence due to the H-2 haplotype, we examined some members of the BXH/Ty set of recombinant inbred mice. The BXH/Ty set was derived by a cross of the normal C75BU6J and the C3H/HeJ strain. The BxH-4/Ty strain was chosen as a hyporesponsive strain and the BxH-14/Ty strain for the normal counterpart. The normal parental strain, C57BI/6J, and the normal BxH-14/Ty strain show patterns consistent with the normal C3H/HeN strain. The reduction of sialidase-sensitive gangliosides (primarily GM1b (cisGM1)) occurs in the endotoxin-hyporesponsive strains, C3H/HeJ and BxH-4/Ty. The hyporesponsive C3H/HeJ parent strain and the normal BXH-14/Ty recombinant strain are H-2 k haplotype whereas the normal C57BI/6J parent strain and the hyporesponsive BXH-4/Ty recombinant strain are H-2 b haplotype. The ganglioside shifts are consistent with a major pleotropic effect of the Lps defect, not H-2 haplotype.