Immunoactivating peptide p4 augments alveolar macrophage phagocytosis in two diverse human populations.
Immunoactivating peptide p4 augments alveolar macrophage phagocytosis in two diverse human populations.
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DOI：
10.1128/aac.00742-13
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发表时间：
2013-09
影响因子：
4.9
通讯作者：
Gordon SB
中科院分区：
文献类型：
--
作者：
Bangert M;Wright AK;Rylance J;Kelly MJ;Wright AD;Carlone GM;Sampson JS;Rajam G;Ades EW;Kadioglu A;Gordon SB
迫切需要新的治疗策略来克服急性细菌感染的早期死亡率。先前的研究表明，在被动免疫疗法的同时给予新型免疫激活肽（P4）可以预防败血症的发生，并将小鼠从肺炎球菌肺炎和败血症的致命侵袭性疾病模型中拯救出来。在这项研究中，我们利用两个不同的成年志愿者群体，确定了人肺泡巨噬细胞的 P4 治疗是否会上调体外对肺炎链球菌的吞噬杀灭作用。我们还测量了刺激后巨噬细胞的细胞内氧化、细胞因子分泌和表面标志物表达。在没有非特异性炎症的情况下，肽治疗显示出增强的细菌杀灭能力，这与治疗潜力一致。这是 P4 对离体人肺细胞功效的首次证明。
New treatment strategies are urgently needed to overcome early mortality in acute bacterial infections. Previous studies have shown that administration of a novel immunoactivating peptide (P4) alongside passive immunotherapy prevents the onset of septicemia and rescues mice from lethal invasive disease models of pneumococcal pneumonia and sepsis. In this study, using two diverse populations of adult volunteers, we determined whether P4 treatment of human alveolar macrophages would upregulate phagocytic killing of Streptococcus pneumoniae ex vivo. We also measured macrophage intracellular oxidation, cytokine secretion, and surface marker expression following stimulation. Peptide treatment showed enhanced bacterial killing in the absence of nonspecific inflammation, consistent with therapeutic potential. This is the first demonstration of P4 efficacy on ex vivo-derived human lung cells.