Immunization with P277 induces vascular leak syndrome in C57BL/6 mice via endothelial damage

Abstract

Accumulating evidence established a positive association of anti-heat shock protein 60 (HSP60) autoantibodies and the presence of atherosclerosis. However, whether anti-P277 (HSP60 437–460) autoantibodies may lead to the pathological increase in vascular permeability, a vascular leak syndrome (VLS), is unknown. In the present study, anti-P277 immunity was effectively induced in C57BL/6 mice, causing a marked increase in VLS in both normal mice and those bearing melanoma as well. Further analysis of the pathological role of anti-P277 immunity revealed that the B-cell epitopes located in P277 played a causal role in the development of VLS. Moreover, studies on endothelial cells (ECs) showed that the anti-P277 antibodies could cross-react with HSP60, highly expressed in both normal and stressed ECs, and mediate damage to cells in the presence of complement. These data suggested that humoral immune response induced by anti-P277 immunity mediates EC damage and induces VLS. These negative effects may cast shadows on P277, used as a peptide vaccine.

Keywords::

• P277 immunization
• vascular leak syndrome
• endothelial damage
• autoimmunity

Declaration of interest: This work was supported by the China National Natural Science Fund Committee (Grant Nos 30500458, 30701023, 30672464, 30572272, and 30772570) and the Natural Science Foundation of Jiangsu Province (No. BK 2007170). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.