可激发自体免疫对抗超级细菌的新型蛋白质
由加拿大英属哥伦比亚大学的免疫学家 Robert Hancock所带领的研究小组，最近研发出一种新的化合物，能够激发起免疫系统的首道防线，使小鼠死于抗药性细菌感染的机率减少。这项研究结果发表于最新一期的Nature Biotechnology中。抗药性细菌引起的疾病是全球性问题，其中威胁最大的是耐万古霉素肠球菌（VRE）和耐甲氧西林金黄色葡萄球菌（MRSA），它们都是普通抗生素无法对付的超级细菌。Hancock等人研究了一组多肽，并且先在小鼠身上进行实验。
结果研究人员发现这些多肽能使败血症有所好转。唯一的问题是它们导致了过敏反应，引起一些健康的肠细胞死亡。因此，Hancock和同事设计出更短的多肽，既能阻止败血症，又不会引起其它并发症。研究人员偶然发现一种13个胺基酸长的多肽，并将此称为先天防御调节器 （Innate Defense Regulator , IDR-1）。为了检验其效果，研究人员将IDR-1注射入小鼠体内，这些小鼠中，有些未感染VRE或MRSA，或是感染不超过4小时。结果发现，这些小鼠存活率是之前的两倍。
研究人员表示，并不是这些多肽直接杀死了超级细菌。而是使人体自体的先天免疫系统事前有了准备，使体内产生过剩的单核白细胞和巨噬细胞，吞噬入侵的病原体。同时，由于体内产生的更具侵略性的噬中性白细胞较少，因此不会导致败血症。IDR-1的临床实验将在12到15个月后开始进行。
(资料来源 : biocompare)
部分英文原文：
Nature Biotechnology，Published online: 25 March 2007; | doi:10.1038/nbt1288
An anti-infective peptide that selectively modulates the innate immune response
Monisha G Scott1, Edie Dullaghan1, 4, Neeloffer Mookherjee2, 4, Natalie Glavas1, Matthew Waldbrook2, Annick Thompson1, Aikun Wang1, Ken Lee1, Silvana Doria2, Pam Hamill2, Jie Jessie Yu2, Yuexin Li2, Oreola Donini1, M Marta Guarna1, B Brett Finlay3, John R North1 & Robert E W Hancock2
1 Inimex Pharmaceuticals Inc., 3650 Wesbrook Mall, Vancouver, British Columbia, Canada V6S 2L2.
2 Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4
3 Michael Smith Laboratories, 2259 Lower Mall Research Station, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4.
4 These authors contributed equally to this work.
Correspondence should be addressed to Robert E W Hancockbob@cmdr.ubc.ca
We show that an innate defense–regulator peptide (IDR-1) was protective in mouse models of infection with important Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and Salmonella enterica serovar Typhimurium. When given from 48 h before to 6 h after infection, the peptide was effective by both local and systemic administration. Because protection by IDR-1 was prevented by in vivo depletion of monocytes and macrophages, but not neutrophils or B- and T-lymphocytes, we conclude that monocytes and macrophages are key effector cells. IDR-1 was not directly antimicrobial: gene and protein expression analysis in human and mouse monocytes and macrophages indicated that IDR-1, acting through mitogen-activated protein kinase and other signaling pathways, enhanced the levels of monocyte chemokines while reducing pro-inflammatory cytokine responses. To our knowledge, an innate defense regulator that counters infection by selective modulation of innate immunity without obvious toxicities has not been reported previously.
摘自《生物谷》
结果研究人员发现这些多肽能使败血症有所好转。唯一的问题是它们导致了过敏反应，引起一些健康的肠细胞死亡。因此，Hancock和同事设计出更短的多肽，既能阻止败血症，又不会引起其它并发症。研究人员偶然发现一种13个胺基酸长的多肽，并将此称为先天防御调节器 （Innate Defense Regulator , IDR-1）。为了检验其效果，研究人员将IDR-1注射入小鼠体内，这些小鼠中，有些未感染VRE或MRSA，或是感染不超过4小时。结果发现，这些小鼠存活率是之前的两倍。
研究人员表示，并不是这些多肽直接杀死了超级细菌。而是使人体自体的先天免疫系统事前有了准备，使体内产生过剩的单核白细胞和巨噬细胞，吞噬入侵的病原体。同时，由于体内产生的更具侵略性的噬中性白细胞较少，因此不会导致败血症。IDR-1的临床实验将在12到15个月后开始进行。
(资料来源 : biocompare)
部分英文原文：
Nature Biotechnology，Published online: 25 March 2007; | doi:10.1038/nbt1288
An anti-infective peptide that selectively modulates the innate immune response
Monisha G Scott1, Edie Dullaghan1, 4, Neeloffer Mookherjee2, 4, Natalie Glavas1, Matthew Waldbrook2, Annick Thompson1, Aikun Wang1, Ken Lee1, Silvana Doria2, Pam Hamill2, Jie Jessie Yu2, Yuexin Li2, Oreola Donini1, M Marta Guarna1, B Brett Finlay3, John R North1 & Robert E W Hancock2
1 Inimex Pharmaceuticals Inc., 3650 Wesbrook Mall, Vancouver, British Columbia, Canada V6S 2L2.
2 Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4
3 Michael Smith Laboratories, 2259 Lower Mall Research Station, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4.
4 These authors contributed equally to this work.
Correspondence should be addressed to Robert E W Hancockbob@cmdr.ubc.ca
We show that an innate defense–regulator peptide (IDR-1) was protective in mouse models of infection with important Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and Salmonella enterica serovar Typhimurium. When given from 48 h before to 6 h after infection, the peptide was effective by both local and systemic administration. Because protection by IDR-1 was prevented by in vivo depletion of monocytes and macrophages, but not neutrophils or B- and T-lymphocytes, we conclude that monocytes and macrophages are key effector cells. IDR-1 was not directly antimicrobial: gene and protein expression analysis in human and mouse monocytes and macrophages indicated that IDR-1, acting through mitogen-activated protein kinase and other signaling pathways, enhanced the levels of monocyte chemokines while reducing pro-inflammatory cytokine responses. To our knowledge, an innate defense regulator that counters infection by selective modulation of innate immunity without obvious toxicities has not been reported previously.
摘自《生物谷》
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