Research and reports in biochemistry最新文献

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Identification of Human Cathelicidin Peptide LL-37 as a Ligand for Macrophage Integrin αMβ2 (Mac-1, CD11b/CD18) that Promotes Phagocytosis by Opsonizing Bacteria. 人抗菌肽LL-37作为巨噬细胞整合素αMβ2 (Mac-1, CD11b/CD18)的配体的鉴定

Research and reports in biochemistry Pub Date : 2016-07-07 DOI: 10.2147/RRBC.S107070

V. Lishko, B. Moreno, Nataly P. Podolnikova, T. Ugarova

{"title":"Identification of Human Cathelicidin Peptide LL-37 as a Ligand for Macrophage Integrin αMβ2 (Mac-1, CD11b/CD18) that Promotes Phagocytosis by Opsonizing Bacteria.","authors":"V. Lishko, B. Moreno, Nataly P. Podolnikova, T. Ugarova","doi":"10.2147/RRBC.S107070","DOIUrl":"https://doi.org/10.2147/RRBC.S107070","url":null,"abstract":"LL-37, a cationic antimicrobial peptide, has numerous immune-modulating effects. However, the identity of a receptor(s) mediating the responses in immune cells remains uncertain. We have recently demonstrated that LL-37 interacts with the αMI-domain of integrin αMβ2 (Mac-1), a major receptor on the surface of myeloid cells, and induces a migratory response in Mac-1-expressing monocyte/macrophages as well as activation of Mac-1 on neutrophils. Here, we show that LL-37 and its C-terminal derivative supported strong adhesion of various Mac-1-expressing cells, including HEK293 cells stably transfected with Mac-1, human U937 monocytic cells and murine IC-21 macrophages. The cell adhesion to LL-37 was partially inhibited by specific Mac-1 antagonists, including mAb against the αM integrin subunit and neutrophil inhibitory factor, and completely blocked when anti-Mac-1 antibodies were combined with heparin, suggesting that cell surface heparan sulfate proteoglycans act cooperatively with integrin Mac-1. Coating both Gram-negative and Gram-positive bacteria with LL-37 significantly potentiated their phagocytosis by macrophages, and this process was blocked by a combination of anti-Mac-1 mAb and heparin. Furthermore, phagocytosis by wild-type murine peritoneal macrophages of LL-37-coated latex beads, a model of foreign surfaces, was several fold higher than that of untreated beads. By contrast, LL-37 failed to augment phagocytosis of beads by Mac-1-deficient macrophages. These results identify LL-37 as a novel ligand for integrin Mac-1 and demonstrate that the interaction between Mac-1 on macrophages and bacteria-bound LL-37 promotes phagocytosis.","PeriodicalId":91164,"journal":{"name":"Research and reports in biochemistry","volume":"2016 6 1","pages":"39-55"},"PeriodicalIF":0.0,"publicationDate":"2016-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/RRBC.S107070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68470191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 37

The TREM2-DAP12 signaling pathway in Nasu-Hakola disease: a molecular genetics perspective. TREM2-DAP12信号通路在纳苏-哈科拉病中的分子遗传学研究

Research and reports in biochemistry Pub Date : 2015-01-01 Epub Date: 2015-03-17 DOI: 10.2147/RRBC.S58057

Junjie Xing, Amanda R Titus, Mary Beth Humphrey

{"title":"The TREM2-DAP12 signaling pathway in Nasu-Hakola disease: a molecular genetics perspective.","authors":"Junjie Xing, Amanda R Titus, Mary Beth Humphrey","doi":"10.2147/RRBC.S58057","DOIUrl":"https://doi.org/10.2147/RRBC.S58057","url":null,"abstract":"Nasu-Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a rare recessively inherited disease that is associated with early dementia and bone cysts with fractures. Here, we review the genetic causes of PLOSL with loss-of-function mutations or deletions in one of two genes, TYROBP and TREM2, encoding for two proteins DNAX-activating protein 12 (DAP12) and triggering receptor expressed on myeloid cells-2 (TREM2). TREM2 and DAP12 form an immunoreceptor signaling complex that mediates myeloid cell, including microglia and osteoclasts, development, activation, and function. Functionally, TREM2-DAP12 mediates osteoclast multi-nucleation, migration, and resorption. In microglia, TREM2-DAP12 participates in recognition and apoptosis of neuronal debris and amyloid deposits. Review of the complex immunoregulatory roles of TREM2-DAP12 in the innate immune system, where it can both promote and inhibit pro-inflammatory responses, is given. Little is known about the function of TREM2-DAP12 in normal brain homeostasis or in pathological central nervous system diseases. Based on the state of the field, genetic testing now aids in diagnosis of PLOSL, but therapeutics and interventions are still under development.","PeriodicalId":91164,"journal":{"name":"Research and reports in biochemistry","volume":"5 ","pages":"89-100"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/RRBC.S58057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34097811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 75

The role of the Wnt signaling pathway in cancer stem cells: prospects for drug development Wnt信号通路在癌症干细胞中的作用:药物开发前景

Research and reports in biochemistry Pub Date : 2014-07-31 DOI: 10.2147/RRBC.S53823

Yong-Mi Kim, M. Kahn

{"title":"The role of the Wnt signaling pathway in cancer stem cells: prospects for drug development","authors":"Yong-Mi Kim, M. Kahn","doi":"10.2147/RRBC.S53823","DOIUrl":"https://doi.org/10.2147/RRBC.S53823","url":null,"abstract":"Cancer stem cells (CSCs), also known as tumor initiating cells are now considered to be the root cause of most if not all cancers, evading treatment and giving rise to disease relapse. They have become a central focus in new drug development. Prospective identification, understanding the key pathways that maintain CSCs, and being able to target CSCs, particularly if the normal stem cell population could be spared, could offer an incredible therapeutic advantage. The Wnt signaling cascade is critically important in stem cell biology, both in homeostatic maintenance of tissues and organs through their respective somatic stem cells and in the CSC/tumor initiating cell population. Aberrant Wnt signaling is associated with a wide array of tumor types. Therefore, the ability to safely target the Wnt signaling pathway offers enormous promise to target CSCs. However, just like the sword of Damocles, significant risks and concerns regarding targeting such a critical pathway in normal stem cell maintenance and tissue homeostasis remain ever present. With this in mind, we review recent efforts in modulating the Wnt signaling cascade and critically analyze therapeutic approaches at various stages of development.","PeriodicalId":91164,"journal":{"name":"Research and reports in biochemistry","volume":"4 1","pages":"1 - 12"},"PeriodicalIF":0.0,"publicationDate":"2014-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/RRBC.S53823","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68470041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 51