{"title":"草酸钙晶体对中性粒细胞蛋白质组和功能的影响：对肾结石的影响。","authors":"Chanettee Lertprapai, Paleerath Peerapen, Visith Thongboonkerd","doi":"10.1186/s12964-025-02345-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The majority of stone formers (87.5-95.9%) exhibit mild to moderate interstitial inflammation surrounding the stone. Neutrophils and neutrophil-derived genes/proteins have been found in renal papillae, stone matrix and urine of calcium oxalate monohydrate (COM) stone formers. However, neutrophil-crystal interactions, especially responses of neutrophils to COM crystals, remained unknown.</p><p><strong>Methods: </strong>This study addressed the effects of COM crystals on neutrophil cellular proteome and functions, including phagocytosis, activation/degranulation, neutrophil extracellular traps (NETs) formation and reactive oxygen species (ROS) production.</p><p><strong>Results: </strong>Label-free quantitative (LFQ) proteomics using nanoLC-ESI-Qq-TOF MS/MS with highly stringent criteria revealed that COM caused altered levels of 22 neutrophil proteins involved mainly in immune responses. Investigating neutrophil innate immune functions using flow cytometry, immunofluorescence/fluorescence imaging, ELISA and dichlorodihydrofluorescein diacetate (DCFH-DA) assay revealed that COM enhanced neutrophil phagocytic activity, NETs formation, activation/degranulation and ROS production. Moreover, secretome (a set of secretory products) from COM-treated neutrophils induced the recruitment of macrophages to phagocytose the COM-treated neutrophils.</p><p><strong>Conclusions: </strong>These findings illustrate the expression and functional responses of neutrophils to COM crystals and implicate the important roles that neutrophils play in nephrolithiasis.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"336"},"PeriodicalIF":8.2000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255060/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effects of calcium oxalate crystals on neutrophil cellular proteome and functions: implications for nephrolithiasis.\",\"authors\":\"Chanettee Lertprapai, Paleerath Peerapen, Visith Thongboonkerd\",\"doi\":\"10.1186/s12964-025-02345-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The majority of stone formers (87.5-95.9%) exhibit mild to moderate interstitial inflammation surrounding the stone. Neutrophils and neutrophil-derived genes/proteins have been found in renal papillae, stone matrix and urine of calcium oxalate monohydrate (COM) stone formers. However, neutrophil-crystal interactions, especially responses of neutrophils to COM crystals, remained unknown.</p><p><strong>Methods: </strong>This study addressed the effects of COM crystals on neutrophil cellular proteome and functions, including phagocytosis, activation/degranulation, neutrophil extracellular traps (NETs) formation and reactive oxygen species (ROS) production.</p><p><strong>Results: </strong>Label-free quantitative (LFQ) proteomics using nanoLC-ESI-Qq-TOF MS/MS with highly stringent criteria revealed that COM caused altered levels of 22 neutrophil proteins involved mainly in immune responses. Investigating neutrophil innate immune functions using flow cytometry, immunofluorescence/fluorescence imaging, ELISA and dichlorodihydrofluorescein diacetate (DCFH-DA) assay revealed that COM enhanced neutrophil phagocytic activity, NETs formation, activation/degranulation and ROS production. Moreover, secretome (a set of secretory products) from COM-treated neutrophils induced the recruitment of macrophages to phagocytose the COM-treated neutrophils.</p><p><strong>Conclusions: </strong>These findings illustrate the expression and functional responses of neutrophils to COM crystals and implicate the important roles that neutrophils play in nephrolithiasis.</p>\",\"PeriodicalId\":55268,\"journal\":{\"name\":\"Cell Communication and Signaling\",\"volume\":\"23 1\",\"pages\":\"336\"},\"PeriodicalIF\":8.2000,\"publicationDate\":\"2025-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255060/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Communication and Signaling\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s12964-025-02345-2\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Communication and Signaling","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12964-025-02345-2","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：大多数结石患者（87.5-95.9%）表现为轻度至中度的结石周围间质炎症。中性粒细胞和中性粒细胞衍生的基因/蛋白已在肾乳头、石基质和草酸钙一水（COM）结石患者的尿液中发现。然而，中性粒细胞与晶体的相互作用，特别是中性粒细胞对COM晶体的反应仍然未知。方法：本研究研究了COM晶体对中性粒细胞蛋白质组和功能的影响，包括吞噬、活化/脱颗粒、中性粒细胞胞外陷阱（NETs）的形成和活性氧（ROS）的产生。结果：采用nanolc - esi - q- tof质谱/质谱进行无标记定量（LFQ）蛋白质组学分析，发现COM引起22种主要参与免疫反应的中性粒细胞蛋白水平改变。利用流式细胞术、免疫荧光/荧光成像、ELISA和二氯二氢荧光素（DCFH-DA）检测中性粒细胞先天免疫功能发现，COM增强了中性粒细胞吞噬活性、NETs形成、活化/脱粒和ROS产生。此外，com处理的中性粒细胞分泌组（一组分泌产物）诱导巨噬细胞募集吞噬com处理的中性粒细胞。结论：这些发现说明了中性粒细胞对COM晶体的表达和功能反应，并暗示中性粒细胞在肾结石中起重要作用。
Effects of calcium oxalate crystals on neutrophil cellular proteome and functions: implications for nephrolithiasis.
Background: The majority of stone formers (87.5-95.9%) exhibit mild to moderate interstitial inflammation surrounding the stone. Neutrophils and neutrophil-derived genes/proteins have been found in renal papillae, stone matrix and urine of calcium oxalate monohydrate (COM) stone formers. However, neutrophil-crystal interactions, especially responses of neutrophils to COM crystals, remained unknown.
Methods: This study addressed the effects of COM crystals on neutrophil cellular proteome and functions, including phagocytosis, activation/degranulation, neutrophil extracellular traps (NETs) formation and reactive oxygen species (ROS) production.
Results: Label-free quantitative (LFQ) proteomics using nanoLC-ESI-Qq-TOF MS/MS with highly stringent criteria revealed that COM caused altered levels of 22 neutrophil proteins involved mainly in immune responses. Investigating neutrophil innate immune functions using flow cytometry, immunofluorescence/fluorescence imaging, ELISA and dichlorodihydrofluorescein diacetate (DCFH-DA) assay revealed that COM enhanced neutrophil phagocytic activity, NETs formation, activation/degranulation and ROS production. Moreover, secretome (a set of secretory products) from COM-treated neutrophils induced the recruitment of macrophages to phagocytose the COM-treated neutrophils.
Conclusions: These findings illustrate the expression and functional responses of neutrophils to COM crystals and implicate the important roles that neutrophils play in nephrolithiasis.
期刊介绍：
Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior.
Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.
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