Properdin Deficiency Impairs Phagocytosis and Enhances Injury at Kidney Repair Phase Post Ischemia-Reperfusion
| Autor: | Zinah Zwaini, Cordula M. Stover, Nigel J. Brunskill, Yuanyuan Wu, Ravinder S. Chana, Bin Yang, Hui Wang, Xinyue Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Phagocytosis Immunology ischemia–reperfusion injury Inflammation chemical and pharmacologic phenomena Apoptosis HMGB1 urologic and male genital diseases Kidney Models Biological Mice Downregulation and upregulation medicine Immunology and Allergy Animals Original Research Mice Knockout biology Properdin Chemistry Macrophages Epithelial Cells RC581-607 Erythropoietin receptor Cell biology Mice Inbred C57BL Disease Models Animal inflammation repair Reperfusion Injury biology.protein Alternative complement pathway medicine.symptom Immunologic diseases. Allergy |
| Zdroj: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | Properdin, a positive regulator of complement alternative pathway, participates in renal ischemia–reperfusion (IR) injury and also acts as a pattern-recognition molecule affecting apoptotic T-cell clearance. However, the role of properdin in tubular epithelial cells (TECs) at the repair phase post IR injury is not well defined. This study revealed that properdin knockout (PKO) mice exhibited greater injury in renal function and histology than wild-type (WT) mice post 72-h IR, with more apoptotic cells and macrophages in tubular lumina, increased active caspase-3 and HMGB1, but better histological structure at 24 h. Raised erythropoietin receptor by IR was furthered by PKOand positively correlated with injury and repair markers. Properdin in WT kidneys was also upregulated by IR, while H2O2-increased properdin in TECs was reduced by its small-interfering RNA (siRNA), with raised HMGB1 and apoptosis. Moreover, the phagocytic ability of WT TECs, analyzed by pHrodoEscherichia colibioparticles, was promoted by H2O2but inhibited by PKO. These results were confirmed by counting phagocytosed H2O2-induced apoptotic TECs byin situend labeling fragmented DNAs but not affected by additional serum with/without properdin. Taken together, PKOresults in impaired phagocytosis at the repair phase post renal IR injury. Properdin locally produced by TECs plays crucial roles in optimizing damaged cells and regulating phagocytic ability of TECs to effectively clear apoptotic cells and reduce inflammation. |
| Databáze: | OpenAIRE |
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