Adhesive Mechanisms of Histone-Induced Neutrophil-Endothelium Interactions in the Muscle Microcirculation
| Autor: | Yongzhi Wang, Lingtao Luo, Johanna Puegge, Jonas Roller, Su Zhang, Henrik Thorlacius, Brigitte Vollmar |
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| Rok vydání: | 2015 |
| Předmět: |
Male
P-selectin Endothelium Neutrophils Integrin Macrophage-1 Antigen Inflammation Histones Mice Cell Movement Cell Adhesion medicine Animals Lymphocyte function-associated antigen 1 Muscle Skeletal Cell adhesion biology Tumor Necrosis Factor-alpha Cell adhesion molecule Chemistry Microcirculation Lymphocyte Function-Associated Antigen-1 Cell biology Mice Inbred C57BL P-Selectin medicine.anatomical_structure Immunology biology.protein Surgery Endothelium Vascular medicine.symptom Selectin |
| Zdroj: | European Surgical Research. 56:19-31 |
| ISSN: | 1421-9921 0014-312X |
| Popis: | Background: Extracellular histones released during cell damage have the capacity to cause tissue injury associated with increased leukocyte accumulation. However, the molecular mechanisms regulating histone-induced leukocyte recruitment remain elusive. The objective of this study was to examine the role of adhesion molecules in histone-dependent leukocyte accumulation by use of intravital microscopy of the mouse cremaster microcirculation. Methods: Histone 3 and TNF-α were intrascrotally administered, and anti-P-selectin, anti-P-selectin glycoprotein ligand-1 (PSGL-1), anti-membrane-activated complex-1 (Mac-1), anti-lymphocyte function antigen-1 (LFA-1) antibody and neutrophil depletion antibody were injected intravenously or intraperitoneally. Results: Intrascrotal injection of histone 3 dose-dependently increased leukocyte recruitment. Neutrophil depletion abolished intravascular and extravascular leukocytes after histone 3 challenge, suggesting that neutrophils were the dominating leukocyte subtype responding to histone stimulation. Pretreatment with an anti-P-selectin and an anti-PSGL-1 antibody abolished histone-stimulated neutrophil rolling, adhesion and emigration. When the anti-P-selectin or the anti-PSGL-1 antibody was administrated after histone 3 stimulation, neutrophil rolling was reduced, whereas the number of firmly adherent and emigrated neutrophils were unchanged, suggesting that the inhibitory effect of blocking P-selectin and PSGL-1 on neutrophil adhesion and recruitment was due to the reduction in neutrophil rolling. Moreover, pretreatment with antibodies against Mac-1 and LFA-1 had no effect of neutrophil rolling but abolished adhesion and emigration evoked by histone 3. Thus, our data demonstrate that P-selectin and PSGL-1 play an important role in histone-induced inflammatory cell recruitment by mediating neutrophil rolling as a precondition for histone-provoked firm adhesion and emigration in vivo. Moreover, we conclude that both Mac-1 and LFA-1 are critical in supporting histone-provoked firm adhesion of neutrophils to endothelial cells. Conclusion: These novel findings define specific selectins and integrins as potential targets for pharmacological intervention in histone-dependent inflammatory diseases. |
| Databáze: | OpenAIRE |
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