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

Abstract

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.

• Authors: Carissa J Ball, Alyssa J Reiffel, Sathvika Chintalapani, Minsoo Kim, Jason A Spector, Michael R King
• Journal: Plastic and reconstructive surgery (Plast Reconstr Surg) Vol. 131 Issue 3 Pg. 487-497 (Mar 2013) ISSN: 1529-4242 [Electronic] United States
• PMID: 23446563 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• L-Selectin
• ADAM Proteins
• ADAM17 Protein
• ADAM17 protein, human
• Adam17 protein, mouse
• Hydrogen Sulfide

Topics

• ADAM Proteins (physiology)
• ADAM17 Protein
• Animals
• Hindlimb (blood supply)
• Hydrogen Sulfide (pharmacology)
• L-Selectin (physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Neutrophil Infiltration (drug effects)
• Reperfusion Injury (immunology)