M. Menschikowski et al., CHANGES IN EPITOPE EXPOSITION OF APOLIPOPROTEIN-A-I ON THE SURFACE OFHIGH-DENSITY-LIPOPROTEINS AFTER PHOSPHOLIPASE A(2) TREATMENT, Atherosclerosis, 117(2), 1995, pp. 159-167
The immunoreactivity of high density lipoproteins (HDL) modified by tr
eatment with porcine pancreatic phospholipase A(2) (PLA2) was studied
in a competitive radioimmunoassay using 6 different monoclonal apolipo
protein (ape) A-I antibodies. The competition tests have shown that af
ter PLA2 treatment the immunoreactivity of selected epitopes of apo A-
I changed in different ways. While the binding behaviour of two epitop
es remained unchanged, three epitopes exhibited decreased immunoreacti
vities after phospholipid hydrolysis. In contrast to the latter epitop
es, the immunoreactivity of an epitope located on the cyanogen bromide
fragment 4 of apo A-I increased with the degree of lipolysis. A loss
of apo A-I from HDL as a consequence of PLA2-treatment did not occur a
s shown by the determination of the apo A-I concentration in HDL befor
e and after treatment with PLA2. Using overlapped synthetic decapeptid
es it could be shown that the epitope increasingly exposed on the part
icle surface of PLA2-modified HDL consists bf the amino acid residues
162-173 and 212-229. These residues are characterized by high hydropho
bic indices as determined by hydropathy analysis. Furthermore, these r
egions belong partially to the proposed receptor-binding domain of apo
A-I. Thus, an increased exposition of this epitope might result in el
evated cellular binding affinities of HDL occurring after modification
of lipoproteins by PLA2-treatment.