Role of C5aR1 and C5L2 Receptors in Ischemia-Reperfusion Injury

• Main Authors: Carlos Arias-Cabrales, Eva Rodriguez-Garcia, Javier Gimeno, David Benito, María José Pérez-Sáez, Dolores Redondo-Pachón, Anna Buxeda, Carla Burballa, Marta Crespo, Marta Riera, Julio Pascual
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Journal of Clinical Medicine
• Subjects: kidney transplant; ischemia-reperfusion injury; delayed graft function; complement system; C5a receptors
• Online Access: https://www.mdpi.com/2077-0383/10/5/974

The role of C5a receptors (C5aR1 and C5L2) in renal ischemia-reperfusion injury (IRI) is uncertain. We generated an in vitro model of hypoxia/reoxygenation with human proximal tubule epithelial cells to mimic some IRI events. C5aR1, membrane attack complex (MAC) and factor H (FH) deposits were evaluated with immunofluorescence. Quantitative polymerase chain reaction evaluated the expression of <i>C5aR1</i>, <i>C5L2</i> genes as well as genes related to tubular injury, inflammation, and profibrotic pathways. Additionally, C5aR1 and C5L2 deposits were evaluated in kidney graft biopsies (KB) from transplant patients with delayed graft function (DGF, <i>n</i> = 12) and compared with a control group (<i>n</i> = 8). We observed higher immunofluorescence expression of C5aR1, MAC and FH as higher expression of genes related to tubular injury, inflammatory and profibrotic pathways and of <i>C5aR1</i> in the hypoxic cells; whereas, <i>C5L2</i> gene expression was unaffected by the hypoxic stimulus. Regarding KB, C5aR1 was detected in the apical and basal membrane of tubular epithelial cells, whereas C5L2 deposits were observed in endothelial cells of peritubular capillaries (PTC). DGF-KB showed more frequently diffuse C5aR1 staining and C5L2 compared to controls. In conclusion, C5aR1 expression is increased by hypoxia and IRI, both in vitro and in human biopsies with an acute injury. C5L2 expression in PTC could be related to endothelial cell damage during IRI.