NEUTROPHIL ACTIVATION ON BIOLOGICAL SURFACES - MASSIVE SECRETION OF HYDROGEN-PEROXIDE IN RESPONSE TO PRODUCTS OF MACROPHAGES AND LYMPHOCYTES
NEUTROPHIL ACTIVATION ON BIOLOGICAL SURFACES - MASSIVE SECRETION OF HYDROGEN-PEROXIDE IN RESPONSE TO PRODUCTS OF MACROPHAGES AND LYMPHOCYTES
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DOI：
10.1172/jci113241
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发表时间：
1987-12-01
影响因子：
15.9
通讯作者：
NATHAN, CF
中科院分区：
文献类型：
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作者：
NATHAN, CF
重组肿瘤坏死因子α（rTNF α）和β（rTNF β.）不会触发悬浮液中PMN释放H2 O2。然而，当中性粒细胞涂在聚苯乙烯表面涂有血清，纤连蛋白，玻连蛋白，层粘连蛋白，或人脐静脉内皮细胞（HUVEC），rTNF诱导大规模的，长期的分泌反应，类似于佛波醇肉豆蔻酸酯乙酸酯（PMA）或细菌引起的。在血清包被的平板上，响应于rTNF α的H2 O2释放的最大持续速率为： 是2.6 +-。0.2每106个PMN的释放速率与PMA相同，持续时间为73 . ±. nmol/min。在层粘连蛋白包被的表面或HUVEC上，响应rTNF的H2 O2释放较慢，但持续约4分钟。3.5 h，达到相同的总量（> 100 nmol/106 PMN）。该反应不仅比用悬浮的PMN研究的呼吸爆发的其它可溶性刺激物长得多且大得多，而且引发rTNF α的半最大反应（EC 50）所需的浓度也比用悬浮的PMN研究的呼吸爆发的其它可溶性刺激物长得多且大得多。的数量级更低（55 pM）。FMLP的应答类似，但重组IFN α的应答范围从零到小，重组IFN β，重组IFN γ，血小板衍生生长因子，重组IL-1 β，或细菌脂多糖。粘附单核细胞不分泌H2 O2响应rTNF或FMLP后15-90分钟，粘附PMN的H2 O2分泌首次检测到。该滞后期不受PMN先前暴露于rTNF α的影响。在悬浮液中，通过在加入rTNF α之前使PMN粘附，或通过在用rTNF α-调节的培养基中孵育粘附的PMN来实现。治疗PMN。细胞松弛素废除H2 O2分泌rTNF的反应，但不是FMLP，如果添加期间，但不是之后，滞后期。因此，从rTNF α-H2 O2分泌处理的PMN似乎是直接但延迟的反应，其需要在暴露于细胞因子期间组装微丝。这些结果表明，粘附到血管内或血管外表面的PMN可能会在巨噬细胞和淋巴细胞对微生物产物和抗原的反应的命令下经历大规模的，长时间的呼吸爆发。
Recombinant tumor necrosis factor alpha (rTNF.alpha.) and beta (rTNF.beta.) did not trigger H2O2 release from PMN in suspension. However, when PMN were plated on polystyrene surfaces coated with serum, fibronectin, vitronectin, laminin, or human umbilical vein endothelial cells (HUVEC), rTNFs induced a massive, prolonged secretory response, similar to that elicited by phorbol myristate acetate (PMA) or bacteria. On serum-coated plates, the maximum sustained rate of H2O2 release in response to rTNF.alpha. was 2.6 .+-. 0.2 nmol/min per 106 PMN, the same as that with PMA; release continued for 73 .+-. 4 min. On laminin-coated surfaces or HUVEC, release of H2O2 in response to rTNFs was slower, but lasted .apprx. 3.5 h, reaching the same total (> 100 nmol/106 PMN). Not only was this response far longer and larger than for other soluble stimuli of the respiratory burst studied with PMN in suspension, but the concentration necessary to elicit a half-maximal response (EC50) for rTNF.alpha. was orders of magnitude lower (55 pM). Responses were similar with FMLP, but ranged from zero to small with recombinant IFN.alpha., recombinant IFN.beta., recombinant IFN.gamma., platelet-derived growth factor, recombinant IL-1.beta., or bacterial lipopolysaccharide. Adherent monocytes did not secrete H2O2 in response to rTNFs H2O2 secretion by adherent PMN was first detectable 15-90 min after addition of rTNFs or FMLP. This lag period was unaffected by prior exposure of PMN to rTNF.alpha. in suspension, by allowing PMN to adhere before adding rTNF.alpha., or by incubating adherent PMN in medium conditioned by rTNF.alpha.-treated PMN. Cytochalasins abolished H2O2 secretion in response to rTNFs, but not FMLP, if added during, but not after, the lag period. Thus, H2O2 secretion from rTNF.alpha.-treated PMN appears to be a direct but delayed response that requires assembly of microfilaments during exposure to the cytokine. These results suggest that PMN adherent to intra- or extravascular surfaces may undergo a massive, prolonged respiratory burst at the command of macrophages and lymphocytes reacting to microbial products and antigens.