硫化氢通过依赖于 L-选择素和 ADAM-17 的方式减少后肢缺血再灌注损伤中的中性粒细胞募集。
Hydrogen sulfide reduces neutrophil recruitment in hind-limb ischemia-reperfusion injury in an L-selectin and ADAM-17-dependent manner.
机构信息
Ithaca, New York, and Rochester, N.Y. From the Department of Biomedical Engineering, Cornell University; the Division of Plastic Surgery, Laboratory of Bioregenerative Medicine and Surgery, Weill Cornell Medical College; and the Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester.
出版信息
Plast Reconstr Surg. 2013 Mar;131(3):487-497. doi: 10.1097/PRS.0b013e31827c6e9c.
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.
背景
缺血后再灌注会导致中性粒细胞浸润到受损组织中。选择素和β2 整合素在中性粒细胞滚动和牢固黏附中调节中性粒细胞与内皮细胞的相互作用。过多的中性粒细胞浸润到组织中被认为会导致缺血再灌注损伤。硫化氢减轻了缺血再灌注损伤造成的损伤。本研究的目的是确定硫化氢对中性粒细胞黏附受体表达的影响。
方法
人中性粒细胞要么未经处理，要么在 20 μM 硫化氢和/或 50 μg/ml 药理学 ADAM-17 抑制剂 TAPI-0 中孵育；通过白细胞介素-8、fMLP 或 TNF-α激活；并用 P-选择素糖蛋白配体-1、白细胞功能相关抗原-1、Mac-1α、L-选择素和β2 整合素表位 CBRM1/5 或 KIM127 进行标记，用于流式细胞术。三组 C57BL/6 小鼠在单侧止血带诱导的后肢缺血 3 小时后接受静脉注射生理盐水载体或 20 μM 硫化氢加或不加 50 μg/ml TAPI-0，然后进行 3 小时再灌注。双侧比目鱼肌在中性粒细胞浸润定量前进行组织学处理。
结果
硫化氢处理以 ADAM-17 依赖性方式显著增加了 fMLP 和白细胞介素-8 激活后人中性粒细胞 L-选择素的脱落。在缺血或再灌注前用硫化氢将血液浓度提高到 20 μM 的小鼠，在止血带诱导的后肢缺血再灌注损伤后，肌肉组织中的中性粒细胞募集明显减少。
结论
硫化氢给药导致激活的人中性粒细胞中 L-选择素表达下调。这导致中性粒细胞渗出和组织浸润减少，这可能部分解释了在缺血再灌注损伤中观察到的硫化氢的保护作用。
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