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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Bromelain treatment decreases neutrophil migration to sites of inflammation.
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Bromelain treatment decreases neutrophil migration to sites of inflammation.

机译：菠萝蛋白酶治疗减少了中性粒细胞向炎症部位的迁移。

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Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain- vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50-85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action.
机译：菠萝蛋白酶是一种源自菠萝茎的蛋白酶混合物，据报道对多种炎性疾病，包括鼠类炎性肠病，都有治疗作用。这项工作的目的是了解这种抗炎活性的潜在机制。已证明在体外暴露于菠萝蛋白酶可去除许多对白细胞运输至关重要的细胞表面分子，包括CD128a / CXCR1和CD128b / CXCR2，它们充当嗜中性白细胞趋化因子IL-8及其鼠同源物的受体。我们假设菠萝蛋白酶可以特异性地蛋白水解去除CD128分子，从而抑制嗜中性粒细胞向IL-8的迁移，从而减少对炎症刺激的急性反应。使用体外趋化性测定，我们证明了响应rhIL-8的菠萝蛋白酶-假处理的人中性粒细胞迁移减少了40％。向细菌肽类似物fMLP的迁移不受影响，表明菠萝蛋白酶不会在白细胞迁移中引起整体缺陷。在三种不同的白细胞迁移到发炎的腹膜腔的鼠模型中，体内菠萝蛋白酶治疗使嗜中性粒细胞迁移减少了50-85％。活体显微镜检查表明，尽管体内菠萝蛋白酶治疗可暂时减少白细胞滚动，但其主要的长期作用是消除白细胞牢固附着在炎症部位的血管上。这些粘附力的变化与对菠萝蛋白酶敏感的CD62L / L-选择素分子的快速重新表达有关，该分子在体内菠萝蛋白酶治疗后介导滚动，并且在所研究的时间内CD128的最小表达。综上所述，这些研究表明菠萝蛋白酶可以有效地减少嗜中性粒细胞向急性炎症部位的迁移，并支持特异性去除CD128趋化因子受体作为潜在的作用机制。

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