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细胞因子及趋化因子蛋白的抗菌作用报道
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antimicrobial agents 通常所指代的是抗生素、抑菌剂、中药、抗菌蛋白等。从2012年以来，科学家陆续发现人体中的多种细胞或蛋白具有体外抗菌或抗病毒能力。 1. MSCs间充质干细胞能够分泌广谱的抗菌肽，该发现开创了抗菌治疗的新思路和新方法。论文链接： Antimicrobial Activity of Mesenchymal Stem Cells: Current Status and New Perspectives of Antimicrobial Peptide-Based Therapies. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28424688/ While mesenchymal stem cells (MSCs)-based therapy appears to be promising, there are concerns regarding possible side effects related to the unwanted suppression of antimicrobial immunity leading to an increased risk of infection. Conversely, recent data show that MSCs exert strong antimicrobial effects through indirect and direct mechanisms, partially mediated by the secretion of antimicrobial peptides and proteins (AMPs). In fact, MSCs have been reported to increase bacterial clearance in preclinical models of sepsis, acute respiratory distress syndrome, and cystic fibrosis-related infections. This article reviews the current evidence regarding the direct antimicrobial effector function of MSCs, focusing mainly on the role of MSCs-derived AMPs. The strategies that might modulate the expression and secretion of these AMPs, leading to enhanced antimicrobial effect, are highlighted. Furthermore, studies evaluating the presence of AMPs in the cargo of extracellular vesicles (EVs) are underlined as perspective opportunities to develop new drug delivery tools. The antimicrobial potential of MSCs-derived EVs can also be heightened through cell conditioning and/or drug loading. Finally, improving the pharmacokinetics and delivery, in addition to deciphering the multi-target drug status of AMPs, should synergistically lead to key advances against infections caused by drug-resistant strains. 2. IFN 分子具有潜在的抗病毒能力。1型IFN是抗病毒防御的细胞因子。近期，学者发现在细菌感染过程中，1型IFN被证实具有抗菌能力。它能够直接杀死MRSA，能够与细菌表面蛋白发生相互作用。IFN被认为是具有抗微生物特性的细胞因子和趋化因子（kinocidins）。论文链接： Direct Antimicrobial Activity of IFN-β http://www.jimmunol.org/content/198/10/4036.long Type I IFNs are a cytokine family essential for antiviral defense. More recently, type I IFNs were shown to be important during bacterial infections. In this article, we show that, in addition to known cytokine functions, IFN-β is antimicrobial. Parts of the IFN-β molecular surface (especially helix 4) are cationic and amphipathic, both classic characteristics of antimicrobial peptides, and we observed that IFN-β can directly kill Staphylococcus aureus Further, a mutant S. aureus that is more sensitive to antimicrobial peptides was killed more efficiently by IFN-β than was the wild-type S. aureus, and immunoblotting showed that IFN-β interacts with the bacterial cell surface. To determine whether specific parts of IFN-β are antimicrobial, we synthesized IFN-β helix 4 and found that it is sufficient to permeate model prokaryotic membranes using synchrotron x-ray diffraction and that it is sufficient to kill S. aureus These results suggest that, in addition to its well-known signaling activity, IFN-β may be directly antimicrobial and be part of a growing family of cytokines and chemokines, called kinocidins, that also have antimicrobial properties. 3. 趋化因子CXC系列分子，均具有抗菌活性。chemokines 通常在免疫反应过程中起到趋化淋巴细胞和其他粒细胞的作用，当然，CXC系列分子也参与了例如干细胞归巢，细胞趋化等大量的细胞生化反应。近期的研究发现，chemokines 具有显著的体外抗菌活性，能够作用于大部分的微生物。原文链接： Antimicrobial chemokines https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438526/ Chemokines are best known for their classic leukocyte chemotactic activity, which is critical for directing the immune response to sites of infection and injury. However, recent studies have suggested that at least some chemokines may also interfere with infectious agents directly. Antimicrobial chemokines tend to contain amphipathic alpha helical secondary structure, and broad-spectrum activity against both Gram-positive and Gram negative bacteria, as well as fungi. Conversely, several bacteria have been identified that possess mechanisms for specifically blocking the antimicrobial activities of chemokines. Although the precise mechanisms by which chemokines and microbes disarm one another in vitro remain unknown, there is now emerging evidence in vivo that such interactions may be biologically significant. More research will be needed to determine whether chemokines with direct antimicrobial activity may be translated into a novel class of antibiotics. 具有抗菌能力的蛋白分子，通常都具有显著的特征，然而具有该特征的分子并非都具有抗菌作用。在体内环境中，这些抗菌肽和抗菌分子的作用机制仍不明确，没有直接证据表明，他们参与了微生物的免疫反应。更多的抗菌研究是必要的，有助于揭示感染性疾病过程中，免疫系统如何参与抗感染作用的。这些抗菌物质的存在，可能预示着抗感染过程具有牵一发而动全身的机制，可能具有大量的靶点可以用于药物介入治疗感染性疾病。 |
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