The development of atherosclerotic lesions in the apoff1 - mouse model of
atherosclerosis is significantly reduced when infected with the blood-living
parasite Schistosoma mansoni. Two infection-dependent effects that may
contribute to a reduction in atherogenesis - the production of anti-platelet
antibodies and a lowering of blood cholesterol levels - were investigated.
An antigen present in mammalian host life-stages of S. mansoni which is crossreactive with mouse and human platelets was investigated in cercarial
transformation fluid (CTF). A 37-43kDa periodate-insensitive antigen which was
reacted against by IgG antibodies in rabbit anti-platelet sera was purified using
chromatographic and electrophoretic methods, but both N-terminal amino-acid
sequencing and attempts to raise antisera against the antigen were nsuccessful.
An antibody monospecific for the 37kDa antigen was therefore affinity-purified
from rabbit anti-platelet antiserum and was found to react against 43k:Da mouse
platelet proteins.
The cross-reactive antigen was subsequently identified as actin by MALDI-TOF
analysis of two-dimensional electrophoresis gels. Confirmation of this identity
and amino-acid sequence information, though, is still required.
Antibody-dependent inhibition of a number of common platelet agonists was
found during aggregometric testing, both with platelets from mice having patent
S. mansoni infections and with normal mouse platelets incubated with the
monospecific antibody. These effects on platelet function could contribute to the
anti-atherogenic effect of infection.
The life-stage responsible for a cholesterol-lowering effect of patent S. mansoni
infections was identified as an aqueous-soluble component of schistosome eggs
that was not present in single-sex, worm-alone S. mansoni infections.
The cholesterol-lowering effect of infection was not diminished in high-fat dietfed T-cell depleted mice, showing that this effect was immune-independent.
Observations that lipid droplets in liver tissue sections from uninfected high-fat
diet-fed mice were mostly absent in samples from the same mice having patent S. mansoni infections may lead to future studies on heart disease associated with "fatty liver".