Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone Suppresses the Secretory Processes That Ensure the Invasion of Neutrophils into Tissues and Induce Inflammation
Integrin-dependent adhesion of neutrophils to tissue, accompanied by the development of neutrophil-induced inflammation, occurs both in the focus of infection and in the absence of infection in metabolic disorders such as reperfusion after ischemia, diabetes mellitus, or the development of pneumonia...
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MDPI AG
2022-01-01
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| author | Svetlana I. Galkina Natalia V. Fedorova Alexander L. Ksenofontov Ekaterina A. Golenkina Marina V. Serebryakova Vladimir I. Stadnichuk Ludmila A. Baratova Galina F. Sud’ina |
| author_facet | Svetlana I. Galkina Natalia V. Fedorova Alexander L. Ksenofontov Ekaterina A. Golenkina Marina V. Serebryakova Vladimir I. Stadnichuk Ludmila A. Baratova Galina F. Sud’ina |
| author_sort | Svetlana I. Galkina |
| collection | DOAJ |
| description | Integrin-dependent adhesion of neutrophils to tissue, accompanied by the development of neutrophil-induced inflammation, occurs both in the focus of infection and in the absence of infection in metabolic disorders such as reperfusion after ischemia, diabetes mellitus, or the development of pneumonia in patients with cystic fibrosis or viral diseases. Hyaluronic acid (HA) plays an important role in the recruitment of neutrophils to tissues. 4-methylumbilliferon (4-MU), an inhibitor of HA synthesis, is used to treat inflammation, but its mechanism of action is unknown. We studied the effect of 4-MU on neutrophil adhesion and concomitant secretion using adhesion to fibronectin as a model for integrin-dependent adhesion. 4-MU reduced the spreading of neutrophils on the substrate and the concomitant secretion of granule proteins, including pro-inflammatory components. 4-MU also selectively blocked adhesion-induced release of the free amino acid hydroxylysine, a product of lysyl hydroxylase, which can influence cell invasion by modifying the extracellular matrix. Finally, 4-MU inhibited the formation of cytonemes, the extracellular membrane secretory structures containing the pro-inflammatory bactericides of the primary granules. The anti-inflammatory effect of 4-MU may be associated with the suppression of secretory processes that ensure the neutrophil invasion and initiate inflammation. We suggest that HA, due to the peculiarities of its synthesis, can promote the release of secretory carriers from the cell and 4-MU can block this process. |
| first_indexed | 2024-03-09T22:32:28Z |
| format | Article |
| id | doaj.art-041802758aeb498bb7f326cab7338001 |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T22:32:28Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-041802758aeb498bb7f326cab73380012023-11-23T18:53:41ZengMDPI AGBiomedicines2227-90592022-01-0110231410.3390/biomedicines10020314Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone Suppresses the Secretory Processes That Ensure the Invasion of Neutrophils into Tissues and Induce InflammationSvetlana I. Galkina0Natalia V. Fedorova1Alexander L. Ksenofontov2Ekaterina A. Golenkina3Marina V. Serebryakova4Vladimir I. Stadnichuk5Ludmila A. Baratova6Galina F. Sud’ina7A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, 119991 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, 119991 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, 119991 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, 119991 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, 119991 Moscow, RussiaPhysical Department, M.V. Lomonosov Moscow State University, 119991 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, 119991 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, 119991 Moscow, RussiaIntegrin-dependent adhesion of neutrophils to tissue, accompanied by the development of neutrophil-induced inflammation, occurs both in the focus of infection and in the absence of infection in metabolic disorders such as reperfusion after ischemia, diabetes mellitus, or the development of pneumonia in patients with cystic fibrosis or viral diseases. Hyaluronic acid (HA) plays an important role in the recruitment of neutrophils to tissues. 4-methylumbilliferon (4-MU), an inhibitor of HA synthesis, is used to treat inflammation, but its mechanism of action is unknown. We studied the effect of 4-MU on neutrophil adhesion and concomitant secretion using adhesion to fibronectin as a model for integrin-dependent adhesion. 4-MU reduced the spreading of neutrophils on the substrate and the concomitant secretion of granule proteins, including pro-inflammatory components. 4-MU also selectively blocked adhesion-induced release of the free amino acid hydroxylysine, a product of lysyl hydroxylase, which can influence cell invasion by modifying the extracellular matrix. Finally, 4-MU inhibited the formation of cytonemes, the extracellular membrane secretory structures containing the pro-inflammatory bactericides of the primary granules. The anti-inflammatory effect of 4-MU may be associated with the suppression of secretory processes that ensure the neutrophil invasion and initiate inflammation. We suggest that HA, due to the peculiarities of its synthesis, can promote the release of secretory carriers from the cell and 4-MU can block this process.https://www.mdpi.com/2227-9059/10/2/3144-methylumbelliferoneneutrophiladhesionsecretionhydroxylysinecytoneme |
| spellingShingle | Svetlana I. Galkina Natalia V. Fedorova Alexander L. Ksenofontov Ekaterina A. Golenkina Marina V. Serebryakova Vladimir I. Stadnichuk Ludmila A. Baratova Galina F. Sud’ina Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone Suppresses the Secretory Processes That Ensure the Invasion of Neutrophils into Tissues and Induce Inflammation Biomedicines 4-methylumbelliferone neutrophil adhesion secretion hydroxylysine cytoneme |
| title | Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone Suppresses the Secretory Processes That Ensure the Invasion of Neutrophils into Tissues and Induce Inflammation |
| title_full | Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone Suppresses the Secretory Processes That Ensure the Invasion of Neutrophils into Tissues and Induce Inflammation |
| title_fullStr | Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone Suppresses the Secretory Processes That Ensure the Invasion of Neutrophils into Tissues and Induce Inflammation |
| title_full_unstemmed | Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone Suppresses the Secretory Processes That Ensure the Invasion of Neutrophils into Tissues and Induce Inflammation |
| title_short | Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone Suppresses the Secretory Processes That Ensure the Invasion of Neutrophils into Tissues and Induce Inflammation |
| title_sort | inhibitor of hyaluronic acid synthesis 4 methylumbelliferone suppresses the secretory processes that ensure the invasion of neutrophils into tissues and induce inflammation |
| topic | 4-methylumbelliferone neutrophil adhesion secretion hydroxylysine cytoneme |
| url | https://www.mdpi.com/2227-9059/10/2/314 |
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