Immunization with P277 induces vascular leak syndrome in C57BL/6 mice via endothelial damage.
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.
Yong
Lu
L
Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, 210009, PR China.
Yunxiao
Sun
S
Qiyan
Xiong
X
Yu
Zhang
Z
Jing
Hou
H
Mekoo
Didier J L
DJ
Fan
Zhang
Z
Xiangbing
Hu
H
Yanjun
Ma
M
Jingjing
Liu
L
Taiming
Li
L
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D002199:Capillary Permeability / Q000276:immunology*; D045744:Cell Line, Tumor; D018834:Chaperonin 60; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D005070:Evans Blue / Q000494:pharmacology; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D007106:Immune Sera / Q000032:analysis; D007114:Immunization / Q000379:methods*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms
D018834:Chaperonin 60; D006360:Heat-Shock Proteins; D007106:Immune Sera; D010446:Peptide Fragments; C095402:peptide 277, heat shock protein 60; D005070:Evans Blue