Hydrogen Sulfide Reduces Neutrophil Recruitment in Hind-Limb Ischemia-Reperfusion Injury in an L-Selectin and ADAM-17–Dependent Manner
Autor: | Michael R. King, Jason A. Spector, Carissa J. Ball, Alyssa J. Reiffel, Sathvika Chintalapani, Minsoo Kim |
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Rok vydání: | 2013 |
Předmět: |
Male
medicine.medical_specialty Endothelium Receptor expression Ischemia ADAM17 Protein Article Mice Internal medicine Animals Medicine Hydrogen Sulfide L-Selectin Neutrophil extravasation biology business.industry medicine.disease Hindlimb Mice Inbred C57BL ADAM Proteins medicine.anatomical_structure Endocrinology Neutrophil Infiltration Reperfusion Injury Immunology biology.protein Surgery L-selectin business Infiltration (medical) Reperfusion injury Selectin |
Zdroj: | Plastic and Reconstructive Surgery. 131:487-497 |
ISSN: | 0032-1052 |
DOI: | 10.1097/prs.0b013e31827c6e9c |
Popis: | Background Reperfusion following ischemia leads to neutrophil recruitment into injured tissue. Selectins and β2-integrins regulate neutrophil interaction with the endothelium during neutrophil rolling and firm adhesion. Excessive neutrophil infiltration into tissue is thought to contribute to ischemia-reperfusion injury damage. Hydrogen sulfide mitigates the damage caused by ischemia-reperfusion injury. This study's objective was to determine the effect of hydrogen sulfide on neutrophil adhesion receptor expression. Methods Human neutrophils were either left untreated or incubated in 20 μM hydrogen sulfide and/or 50 μg/ml pharmacologic ADAM-17 inhibitor TAPI-0; activated by interleukin-8, fMLP, or TNF-α; and labeled against P-selectin glycoprotein ligand-1, leukocyte function associated antigen-1, Mac-1 α, L-selectin, and β2-integrin epitopes CBRM1/5 or KIM127 for flow cytometry. Cohorts of three C57BL/6 mice received an intravenous dose of saline vehicle or 20 μM hydrogen sulfide with or without 50 μg/ml TAPI-0 before unilateral tourniquet-induced hind-limb ischemia for 3 hours followed by 3 hours of reperfusion. Bilateral gastrocnemius muscles were processed for histology before neutrophil infiltration quantification. Results Hydrogen sulfide treatment significantly increased L-selectin shedding from human neutrophils following activation by fMLP and interleukin-8 in an ADAM-17-dependent manner. Mice treated with hydrogen sulfide to raise bloodstream concentration by 20 μM before ischemia or reperfusion showed a significant reduction in neutrophil recruitment into skeletal muscle tissue following tourniquet-induced hind-limb ischemia-reperfusion injury. Conclusions Hydrogen sulfide administration results in the down-regulation of L-selectin expression in activated human neutrophils. This leads to a reduction in neutrophil extravasation and tissue infiltration and may partially account for the protective effects of hydrogen sulfide seen in the setting of ischemia-reperfusion injury. |
Databáze: | OpenAIRE |
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