Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells
Background/Aims: Healing of mesangioproliferative glomerulonephritis involves degradation of excess extracellular matrix, resolution of hypercellularity by apoptosis and phagocytosis of apoptotic cells. Integrin receptors participate in the regulation of phagocytosis. In mice deficient for alpha8 in...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2018-03-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/488160 |
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| author | Ines Marek Robert Becker Fabian B. Fahlbusch Carlos Menendez-Castro Wolfgang Rascher Christoph Daniel Gudrun Volkert Andrea Hartner |
| author_facet | Ines Marek Robert Becker Fabian B. Fahlbusch Carlos Menendez-Castro Wolfgang Rascher Christoph Daniel Gudrun Volkert Andrea Hartner |
| author_sort | Ines Marek |
| collection | DOAJ |
| description | Background/Aims: Healing of mesangioproliferative glomerulonephritis involves degradation of excess extracellular matrix, resolution of hypercellularity by apoptosis and phagocytosis of apoptotic cells. Integrin receptors participate in the regulation of phagocytosis. In mice deficient for alpha8 integrin (Itga8-/-) healing of glomerulonephritis is delayed. As Itga8 is abundant in mesangial cells (MC) which are non-professional phagocytes, we hypothesized that Itga8 facilitates phagocytosis of apoptotic cells and matrix components by MC. Methods: MC were isolated from wild type (WT) and Itga8-/- mice. Latex beads were coated with matrix components. Apoptosis was induced by cisplatin in macrophages and in DiI-stained MC. After coincubation of latex beads or apoptotic cells with MC, the phagocytosis rate was detected in WT and Itga8-/- MC via fluorescence microscopy and FACS analysis. Results: Itga8-/- MC showed reduced phagocytosis of matrix-coated beads and apoptotic cells compared to WT MC. Reduction of stress fibers was observed in Itga8-/- compared to WT MC. Inhibition of cytoskeletal reorganization by inhibition of Rac1 or ROCK during phagocytosis significantly decreased the rate of phagocytosis by WT MC but not by Itga8-/- MC. Conclusion: The expression of Itga8 facilitates phagocytosis in MC, likely mediated by Itga8-cytoskeleton interactions. An impairment of MC phagocytosis might thus contribute to a delayed glomerular regeneration in Itga8-/- mice. |
| first_indexed | 2024-12-11T19:18:46Z |
| format | Article |
| id | doaj.art-6f2d9f40ab014d76866c9d49df9e15fd |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-11T19:18:46Z |
| publishDate | 2018-03-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-6f2d9f40ab014d76866c9d49df9e15fd2022-12-22T00:53:35ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-03-014562161217310.1159/000488160488160Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial CellsInes MarekRobert BeckerFabian B. FahlbuschCarlos Menendez-CastroWolfgang RascherChristoph DanielGudrun VolkertAndrea HartnerBackground/Aims: Healing of mesangioproliferative glomerulonephritis involves degradation of excess extracellular matrix, resolution of hypercellularity by apoptosis and phagocytosis of apoptotic cells. Integrin receptors participate in the regulation of phagocytosis. In mice deficient for alpha8 integrin (Itga8-/-) healing of glomerulonephritis is delayed. As Itga8 is abundant in mesangial cells (MC) which are non-professional phagocytes, we hypothesized that Itga8 facilitates phagocytosis of apoptotic cells and matrix components by MC. Methods: MC were isolated from wild type (WT) and Itga8-/- mice. Latex beads were coated with matrix components. Apoptosis was induced by cisplatin in macrophages and in DiI-stained MC. After coincubation of latex beads or apoptotic cells with MC, the phagocytosis rate was detected in WT and Itga8-/- MC via fluorescence microscopy and FACS analysis. Results: Itga8-/- MC showed reduced phagocytosis of matrix-coated beads and apoptotic cells compared to WT MC. Reduction of stress fibers was observed in Itga8-/- compared to WT MC. Inhibition of cytoskeletal reorganization by inhibition of Rac1 or ROCK during phagocytosis significantly decreased the rate of phagocytosis by WT MC but not by Itga8-/- MC. Conclusion: The expression of Itga8 facilitates phagocytosis in MC, likely mediated by Itga8-cytoskeleton interactions. An impairment of MC phagocytosis might thus contribute to a delayed glomerular regeneration in Itga8-/- mice.https://www.karger.com/Article/FullText/488160Alpha8 integrinItga8PhagocytosisMesangial cellsExtracellular matrix resolutionCytoskeletonGlomerulonephritis |
| spellingShingle | Ines Marek Robert Becker Fabian B. Fahlbusch Carlos Menendez-Castro Wolfgang Rascher Christoph Daniel Gudrun Volkert Andrea Hartner Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells Cellular Physiology and Biochemistry Alpha8 integrin Itga8 Phagocytosis Mesangial cells Extracellular matrix resolution Cytoskeleton Glomerulonephritis |
| title | Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells |
| title_full | Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells |
| title_fullStr | Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells |
| title_full_unstemmed | Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells |
| title_short | Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells |
| title_sort | expression of the alpha8 integrin chain facilitates phagocytosis by renal mesangial cells |
| topic | Alpha8 integrin Itga8 Phagocytosis Mesangial cells Extracellular matrix resolution Cytoskeleton Glomerulonephritis |
| url | https://www.karger.com/Article/FullText/488160 |
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