M. Matic et al., MONOCLONAL-ANTIBODY TO HEPARAN-SULFATE FROM AUTOIMMUNE TIGHT-SKIN (TSK) MICE BINDS TO THE ENDOTHELIAL-CELL SURFACE, Immunological investigations, 26(3), 1997, pp. 371-381
Heparan sulfate proteoglycans have pleiotropic functions in the normal
vasculature. Autoimmunity to heparan sulfate may play a role in vascu
lar injury. In this study, monoclonal antibody (mb) 28C3-1 to heparan
sulfate derived from autoimmune Tight skin (TSK) mice was investigated
for its reactivity with endothelial cells. Mb 28C3-1 was previously d
emonstrated to inhibit the heparin-accelerated formation of antithromb
in III-thrombin complexes. In the current studies it is shown that mAb
28C3-1 bound to heparan sulfate proteoglycan with the highest affinit
y in direct binding solid phase radioimmunoassay. Binding to the hepar
an sulfate was stronger than binding to the protein core, indicating t
hat the primary epitope of 28C3-1 is the polysaccharide component. Usi
ng confocal fluorescent microscopy, mAb 28C3-1 was demonstrated to bin
d to the endothelial cell surface. Furthermore, treatment of endotheli
al cells with heparitinase abolished mAb 28C3-1 binding. These studies
support the hypothesis that naturally occurring anti-heparan sulfate
autoantibodies from autoimmune mice may cause vascular injury by initi
al interaction with endothelial cell surface heparan sulfate.