Mac-1 (CD11b/CD18) mediates adherence-dependent hydrogen peroxide production by human and canine neutrophils.
Mac-1 (CD11b/CD18) mediates adherence-dependent hydrogen peroxide production by human and canine neutrophils.
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DOI：
10.4049/jimmunol.144.7.2702
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发表时间：
1990-04
影响因子：
4.4
通讯作者：
S. Shappell;C. Toman;D. Anderson;A. Taylor;M. Entman;C. Smith
中科院分区：
文献类型：
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作者：
S. Shappell;C. Toman;D. Anderson;A. Taylor;M. Entman;C. Smith
人的中性粒细胞暴露在蛋白包被的聚苯乙烯或培养的内皮单层中，会产生大量的过氧化氢，以响应可溶性刺激，导致悬浮细胞很少或根本不分泌活性氧物种。为了研究这种黏附依赖性呼吸爆发的机制，我们研究了一种已知参与中性粒细胞与内皮细胞黏附的整合素CD11b/CD18(Mac-1)的可能作用。用趋化因子刺激的人和犬中性粒细胞暴露在蛋白涂层表面，以及培养的人和犬内皮细胞来检测过氧化氢的产生。使用的两种蛋白涂层表面是I型胶原涂层玻璃或塑料，人和犬中性粒细胞均不附着的表面，以及锁孔帽状血蓝蛋白(KLH)涂层玻璃或塑料，人和犬中性粒细胞仅在趋化刺激后才附着在其表面。FMLP刺激的人中性粒细胞和血小板激活因子刺激的犬中性粒细胞与I型胶原接触时不能产生可检测到的过氧化氢，但当与KLH或内皮细胞单层黏附时分泌大量的过氧化氢。CD18缺乏症患者的FMLP刺激的中性粒细胞不能附着在这些表面上，在这些条件下也不能产生过氧化氢。与CD18和CD11b反应的单抗在显著抑制正常人中性粒细胞与这些表面的黏附方面同样有效，并显著抑制过氧化氢的产生。与CD18结合的单抗可阻断刺激的犬中性粒细胞的黏附，针对CD18和CD11b的单抗可阻断犬中性粒细胞在KLH和内皮细胞上产生H_2O_2。非结合单抗和与CD11a结合的单抗不抑制人细胞在K1H或内皮细胞单层上产生H_2O_2，非结合和结合对照单抗对犬中性粒细胞产生H_2O_2无抑制作用。这些结果表明，Mac-1(CD11b/CD18)可介导趋化因子刺激的人和犬中性粒细胞产生黏附依赖的H_2O_2。
Human neutrophils exposed to protein-coated polystyrene or cultured endothelial monolayers produce large quantities of H2O2 in response to soluble stimuli that elicit little or no secretion of reactive oxygen species from cells in suspension. To characterize the mechanisms involved in this adherence-dependent respiratory burst, we have investigated the possible role of one integrin known to participate in the adhesion of neutrophils to endothelial cells, CD11b/CD18 (Mac-1). H2O2 production was examined with chemotactic factor-stimulated human and canine neutrophils exposed to protein-coated surfaces and cultured human and canine endothelial cells. The two protein-coated surfaces used were type I collagen-coated glass or plastic, a surface to which neither human nor canine neutrophils adhered, and keyhole limpet hemocyanin (KLH)-coated glass or plastic, a surface to which human and canine neutrophils adhered only after chemotactic stimulation. FMLP-stimulated human neutrophils and platelet activating factor-stimulated canine neutrophils failed to produce detectable H2O2 when in contact with type I collagen, but secreted large amounts of H2O2 when adherent to KLH or endothelial cell monolayers. FMLP-stimulated neutrophils from patients with CD18-deficiency failed to adhere to any of these surfaces and failed to produce H2O2 under these conditions. mAb reactive with CD18 and CD11b were equally effective in markedly inhibiting the adhesion of normal human neutrophils to these surfaces and markedly inhibited the production of H2O2. A mAb reactive with CD18 blocked adhesion of stimulated canine neutrophils, and mAb directed against both CD18 and CD11b blocked H2O2 production by canine neutrophils on KLH and endothelium. A nonbinding mAb and a mAb reactive with CD11a did not inhibit H2O2 production of human cells on KLH or endothelial monolayers, and nonbinding and binding control mAb did not inhibit H2O2 production by canine neutrophils. These results indicate that Mac-1 (CD11b/CD18) can mediate adhesion-dependent H2O2 production by human and canine neutrophils exposed to chemotactic factors.