CXCL1-Triggered Interaction of LFA1 and ICAM1 Control Glucose-Induced Leukocyte Recruitment during Inflammation In Vivo
It is well acknowledged that proinflammatory stimulation during acute hyperglycemia is able to aggravate inflammatory diseases. However, the mechanisms of proinflammatory effects of glucose are controversially discussed. We investigated leukocyte recruitment after intravenous injection of glucose in...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2012/739176 |
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| author | Kirsten Buschmann Lutz Koch Natascha Braach Hanna Mueller David Frommhold Johannes Poeschl Peter Ruef |
| author_facet | Kirsten Buschmann Lutz Koch Natascha Braach Hanna Mueller David Frommhold Johannes Poeschl Peter Ruef |
| author_sort | Kirsten Buschmann |
| collection | DOAJ |
| description | It is well acknowledged that proinflammatory stimulation during acute hyperglycemia is able to aggravate inflammatory diseases. However, the mechanisms of proinflammatory effects of glucose are controversially discussed. We investigated leukocyte recruitment after intravenous injection of glucose in different inflammatory models using intravital microscopy. Flow chamber experiments, expression analysis, functional depletion, and knockout of key adhesion molecules gave mechanistic insight in involved pathways.
We demonstrated that a single injection of glucose rapidly increased blood glucose levels in a dose-dependent manner. Notably, during tumor necrosis factor (TNF) α-induced inflammation leukocyte recruitment was not further enhanced by glucose administration, whereas glucose injection profoundly augmented leukocyte adhesion and transmigration into inflamed tissue in the trauma model, indicating that proinflammatory properties of glucose are stimulus dependent. Experiments with functional or genetic inhibition of the chemokine receptor CXCR2, intercellular adhesion molecule 1 (ICAM1), and lymphocyte function antigen 1 (LFA1) suggest that keratino-derived-chemokine CXCL1-triggered interactions of ICAM1 and LFA1 are crucially involved in the trauma model of inflammation. The lacking effect of glucose on β2 integrin expression and on leukocyte adhesion in dynamic flow chamber experiments argues against leukocyte-driven underlying mechanisms and favours an endothelial pathway since endothelial ICAM1 expression was significantly upregulated in response to glucose. |
| format | Article |
| id | doaj-art-2a8f312ab1a54be0820d946759f9f057 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-2a8f312ab1a54be0820d946759f9f0572025-02-03T01:33:28ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/739176739176CXCL1-Triggered Interaction of LFA1 and ICAM1 Control Glucose-Induced Leukocyte Recruitment during Inflammation In VivoKirsten Buschmann0Lutz Koch1Natascha Braach2Hanna Mueller3David Frommhold4Johannes Poeschl5Peter Ruef6Clinic of Neonatology, Department of Pediatrics, University of Heidelberg, 69120 Heidelberg, GermanyClinic of Neonatology, Department of Pediatrics, University of Heidelberg, 69120 Heidelberg, GermanyClinic of Neonatology, Department of Pediatrics, University of Heidelberg, 69120 Heidelberg, GermanyClinic of Neonatology, Department of Pediatrics, University of Heidelberg, 69120 Heidelberg, GermanyClinic of Neonatology, Department of Pediatrics, University of Heidelberg, 69120 Heidelberg, GermanyClinic of Neonatology, Department of Pediatrics, University of Heidelberg, 69120 Heidelberg, GermanyClinic of Neonatology, Department of Pediatrics, University of Heidelberg, 69120 Heidelberg, GermanyIt is well acknowledged that proinflammatory stimulation during acute hyperglycemia is able to aggravate inflammatory diseases. However, the mechanisms of proinflammatory effects of glucose are controversially discussed. We investigated leukocyte recruitment after intravenous injection of glucose in different inflammatory models using intravital microscopy. Flow chamber experiments, expression analysis, functional depletion, and knockout of key adhesion molecules gave mechanistic insight in involved pathways. We demonstrated that a single injection of glucose rapidly increased blood glucose levels in a dose-dependent manner. Notably, during tumor necrosis factor (TNF) α-induced inflammation leukocyte recruitment was not further enhanced by glucose administration, whereas glucose injection profoundly augmented leukocyte adhesion and transmigration into inflamed tissue in the trauma model, indicating that proinflammatory properties of glucose are stimulus dependent. Experiments with functional or genetic inhibition of the chemokine receptor CXCR2, intercellular adhesion molecule 1 (ICAM1), and lymphocyte function antigen 1 (LFA1) suggest that keratino-derived-chemokine CXCL1-triggered interactions of ICAM1 and LFA1 are crucially involved in the trauma model of inflammation. The lacking effect of glucose on β2 integrin expression and on leukocyte adhesion in dynamic flow chamber experiments argues against leukocyte-driven underlying mechanisms and favours an endothelial pathway since endothelial ICAM1 expression was significantly upregulated in response to glucose.http://dx.doi.org/10.1155/2012/739176 |
| spellingShingle | Kirsten Buschmann Lutz Koch Natascha Braach Hanna Mueller David Frommhold Johannes Poeschl Peter Ruef CXCL1-Triggered Interaction of LFA1 and ICAM1 Control Glucose-Induced Leukocyte Recruitment during Inflammation In Vivo Mediators of Inflammation |
| title | CXCL1-Triggered Interaction of LFA1 and ICAM1 Control Glucose-Induced Leukocyte Recruitment during Inflammation In Vivo |
| title_full | CXCL1-Triggered Interaction of LFA1 and ICAM1 Control Glucose-Induced Leukocyte Recruitment during Inflammation In Vivo |
| title_fullStr | CXCL1-Triggered Interaction of LFA1 and ICAM1 Control Glucose-Induced Leukocyte Recruitment during Inflammation In Vivo |
| title_full_unstemmed | CXCL1-Triggered Interaction of LFA1 and ICAM1 Control Glucose-Induced Leukocyte Recruitment during Inflammation In Vivo |
| title_short | CXCL1-Triggered Interaction of LFA1 and ICAM1 Control Glucose-Induced Leukocyte Recruitment during Inflammation In Vivo |
| title_sort | cxcl1 triggered interaction of lfa1 and icam1 control glucose induced leukocyte recruitment during inflammation in vivo |
| url | http://dx.doi.org/10.1155/2012/739176 |
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