Open AccessPentraxin-3-mediated complement activation in a swine model of renal ischemia/reperfusion injury
Author(s) -
Chiara Divella,
Alessandra Stasi,
Rossana Franzin,
Michele Rossini,
Paola Pontrelli,
Fabio Sallustio,
Giuseppe Stefano Netti,
Elena Ranieri,
Luca Lacitignola,
Francesco Staffieri,
Antonio Crovace,
Giuseppe Lucarelli,
Pasquale Ditonno,
Michele Battaglia,
Mohamed R. Daha,
Pieter van der Pol,
Cees van Kooten,
Giuseppe Grandaliano,
Loreto Gesualdo,
Giovanni Stallone,
Giuseppe Castellano
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202992
Subject(s) - complement system , reperfusion injury , complement (music) , ischemia , renal injury , renal ischemia , medicine , cardiology , immunology , kidney , chemistry , immune system , biochemistry , complementation , gene , phenotype
Pentraxins are a family of evolutionarily conserved pattern recognition molecules with pivotal roles in innate immunity and inflammation, such as opsonization of pathogens during bacterial and viral infections. In particular, the long Pentraxin 3 (PTX3) has been shown to regulate several aspects of vascular and tissue inflammation during solid organ transplantation. Our study investigated the role of PTX3 as possible modulator of Complement activation in a swine model of renal ischemia/reperfusion (I/R) injury. We demonstrated that I/R injury induced early PTX3 deposits at peritubular and glomerular capillary levels. Confocal laser scanning microscopy revealed PTX3 deposits co-localizing with CD31 + endothelial cells. In addition, PTX3 was associated with infiltrating macrophages (CD163), dendritic cells (SWC3a) and myofibroblasts (FSP1). In particular, we demonstrated a significant PTX3-mediated activation of classical (C1q-mediated) and lectin (MBL-mediated) pathways of Complement. Interestingly, PTX3 deposits co-localized with activation of the terminal Complement complex (C5b-9) on endothelial cells, indicating that PTX3-mediated Complement activation occurred mainly at the renal vascular level. In conclusion, these data indicate that PTX3 might be a potential therapeutic target to prevent Complement-induced I/R injury.