Dataset Information

Hydrogen sulfide reduces neutrophil recruitment in hind-limb ischemia-reperfusion injury in an L-selectin and ADAM-17-dependent manner.

ABSTRACT: Reperfusion following ischemia leads to neutrophil recruitment into injured tissue. Selectins and ?2-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.Human neutrophils were either left untreated or incubated in 20 ?M hydrogen sulfide and/or 50 ?g/ml pharmacologic ADAM-17 inhibitor TAPI-0; activated by interleukin-8, fMLP, or TNF-?; and labeled against P-selectin glycoprotein ligand-1, leukocyte function associated antigen-1, Mac-1 ?, L-selectin, and ?2-integrin epitopes CBRM1/5 or KIM127 for flow cytometry. Cohorts of three C57BL/6 mice received an intravenous dose of saline vehicle or 20 ?M hydrogen sulfide with or without 50 ?g/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.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 ?M before ischemia or reperfusion showed a significant reduction in neutrophil recruitment into skeletal muscle tissue following tourniquet-induced hind-limb ischemia-reperfusion injury.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.

SUBMITTER: Ball CJ

PROVIDER: S-EPMC3587315 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hydrogen sulfide reduces neutrophil recruitment in hind-limb ischemia-reperfusion injury in an L-selectin and ADAM-17-dependent manner.

Ball Carissa J CJ Reiffel Alyssa J AJ Chintalapani Sathvika S Kim Minsoo M Spector Jason A JA King Michael R MR

Plastic and reconstructive surgery 20130301 3

<h4>Background</h4>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 ...[more]

PMID: 23446563

Similar Datasets

Project description:Acute ischemia reperfusion injury in skeletal muscle remains an important issue in several fields of regenerative medicine. Thus, a valid model is essential to gain deeper insights into pathophysiological relations and evaluate possible treatment options. While the vascular anatomy of mice regularly prevents sufficient vessel occlusion by invasive methods, there is a multitude of existing models to induce ischemia reperfusion injury without surgical procedures. Since there is no consensus on which model to prefer, this study aims to develop and evaluate a novel, optimized low-pressure tourniquet model. C57BL/6 mice underwent an ischemic procedure by either tourniquet or invasive artery clamping. A sham group served as control. With exception of the sham group, mice underwent 2 hours of ischemia followed by 4 hours of reperfusion. Groups were compared using microcirculatory and spectroscopic measurements, distinctions in tissue edema, histological and immunohistochemical analyses. Both procedures led to a significant decrease in tissue blood flow (- 97% vs. - 86%) and oxygenation (- 87% vs. - 75%) with a superiority of the low-pressure tourniquet. Tissue edema in the tourniquet cohort was significantly increased (+ 59%), while the increase in the clamping cohort was non-significant (+ 7%). Haematoxylin Eosin staining showed significantly more impaired muscle fibers in the tourniquet group (+ 77 p.p. vs. + 11 p.p.) and increased neutrophil infiltration/ROI (+ 51 vs. + 8). Immunofluorescence demonstrated an equal increase of p38 in both groups (7-fold vs. 8-fold), while the increase in apoptotic markers (Caspase-3, 3-Nitrotyrosine, 4-Hydroxynonenal) was significantly higher in the tourniquet group. The low-pressure tourniquet has been proven to produce reproducible and thus reliable ischemia reperfusion injury. In addition, significantly less force was needed than previously stated. It is therefore an important instrument for studying the pathophysiology of ischemia reperfusion injury and for the development of prophylactic as well as therapeutic interventions.

Dataset Information

Hydrogen sulfide reduces neutrophil recruitment in hind-limb ischemia-reperfusion injury in an L-selectin and ADAM-17-dependent manner.

Publications

Hydrogen sulfide reduces neutrophil recruitment in hind-limb ischemia-reperfusion injury in an L-selectin and ADAM-17-dependent manner.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets