中性粒细胞胞外诱捕网的形成机制及在肝病中的作用

中性粒细胞胞外诱捕网(NETs)是近年来新发现的中性粒细胞杀灭病原体的一种新的免疫机制。NETs的主要成分是DNA,上面附着大小不一的颗粒蛋白。NETs在肝缺血再灌注损伤、慢性乙型肝炎、肝硬化和肝癌等肝病中扮演着不同的角色。阐述了NETs的形成机制、结构组成和其在肝病中作用的研究进展。     

中性粒细胞胞外陷阱在肾脏疾病中的研究进展

中性粒细胞胞外陷阱(NETs)是一种由染色质和多种颗粒蛋白组成的细胞外网状结构。形成NETs是中性粒细胞的一种新型死亡方式, 亦是一种新型作用机制。研究表明, NETs能杀灭多种病原体。然而, NETs亦通过不同的作用参与多种疾病的发生发展, 肾脏是NETs主要累及的器官之一。本文就NETs 的形成及其在多种肾脏疾病中的研究进展进行综述, 为肾脏疾病的治疗提供新思路。     

中性粒细胞胞外诱捕网在寄生虫感染中的作用和机制研究进展

中性粒细胞胞外诱捕网（NET）是中性粒细胞胞内染色质与颗粒蛋白结合后释放至胞外所形成的网状结构。研究表明，原虫和蠕虫等寄生虫感染可诱导NET形成，并在抗寄生虫的免疫防御与寄生虫感染引起的免疫病理中发挥重要作用。本文综述了NET在常见原虫和蠕虫感染中的形成机制及其作用的最新研究进展，旨在为寄生虫病预防与治疗提供新思路。     

NETs与心血管疾病的相关研究

中性粒细胞胞外诱捕网(NETs)是活化的中性粒细胞所释放的去聚化染色质DNA和多种抗菌蛋白所组成的纤维网状复合物。NETs可参与机体免疫应答限制病原菌，并导致组织及器官损伤，现有研究发现NETs可参与到动静脉的血栓形成。本文对NETs的结构、发生机制、重要成分及在动脉粥样硬化及血栓中的作用进行综述。     

中性粒细胞胞外诱捕网在系统性红斑狼疮相关间质性肺病中的作用

中性粒细胞参与病原体清除与早期炎症反应,是免疫系统的重要组成部分。但近年来越来越多的研究表明,中性粒细胞通过形成中性粒细胞胞外诱捕网(NETs)介导炎症反应并促进纤维化的形成,在自身免疫性疾病和间质性肺病(ILD)的发病机制中的作用逐渐受到重视。本文首先介绍NETs的结构、功能和形成过程,并结合NETs在其他自身免疫病中的作用,总结NETs参与系统性红斑狼疮(SLE)相关ILD针对NETs的发病机制,最后提出了自身免疫性疾病相关ILD针对NETs的潜在治疗靶点。     

中性粒细胞胞外诱捕网在病毒性心肌炎中的作用

病毒性心肌炎(VMC)是临床常见的心血管疾病,炎症免疫应答是VMC的主要发病病因。中性粒细胞作为先天免疫应答的一部分在VMC中发挥的作用过去很少被研究。然而多个研究表明,中性粒细胞可通过一种新的防御机制即中性粒细胞胞外诱捕网(NETs)的形成参与多种疾病。并且,最近在活动性心肌炎患者和VMC模型心肌病理活检中都发现有NETs形成,因此NETs被推测在VMC发病过程中发挥一定作用。本文就NETs在VMC中的作用作一综述。     

中性粒细胞胞外诱捕网与心血管疾病

中性粒细胞胞外诱捕网（NETs）是中性粒细胞活化或凋亡时释放的一种具有多种生物学活性的网状结构。随着NETs生成和作用机制的阐明,已发现其具有抗炎、促凝、抗凝及加重血管内皮功能障碍等作用。心血管疾病的发生与炎症反应、血液高凝状态等有关。早期检测NETs可能对某些心血管疾病的预防和治疗有重要意义。本文就NETs及其与心血管疾病关系的研究进展进行综述。     

中性粒细胞胞外诱捕网在冠心病发病机制中作用研究的进展

中性粒细胞胞外诱捕网(NETs)是新发现的中性粒细胞杀灭病原体的一个机制。有研究发现NETs还具有促凝和促血栓形成的作用。近期有研究表明,在急性冠脉综合征中,梗死相关血管病变部位的NETs负荷与梗塞的面积呈正相关,本文将就NETs及其在冠心病中的作用作一综述。     

中性粒细胞胞外诱捕网与结直肠癌关系的研究进展

［摘要］　中性粒细胞胞外诱捕网(NETs)是中性粒细胞释放的一种纤维网状结构,其形成过程称为NETosis。近年研究发现,NETs能够促进结直肠癌的增殖、转移和复发,与结直肠癌的预后密切相关。该文对NETs与结直肠癌的关系作一综述,进一步了解NETs在结直肠癌中的作用机制和临床价值。     

中性粒细胞胞外诱捕网的作用机制及其在多种疾病中作用的研究进展

中性粒细胞胞外诱捕网(NETs)是中性粒细胞发挥生物学作用的另一种表现形式。除了具有强大的抗感染作用以外,它亦对机体产生直接或者间接的损伤,可与炎症因子相比拟。近年来研究表明NETs在抗炎、血栓形成、自身抗体的产生等方面均有参与。本文就NETs的基本组成结构以及在多种疾病发生、发展中的作用作一综述。     

Mast cells in allergy and host defense.

Mast cells have been implicated in the pathogenesis of allergic diseases and in inflammatory responses associated with pathological immune and disease-related processes including fibrosis, autoimmune pathology, and neoplasia. Recent findings in animal models of bacterial infection also suggest that mast cells may have a protective role in host defense against pathogens in innate immunity along with the probable role of mast cells in acquired immunity against parasitic infections. Mast cells are strategically located at the host-environment interface and may provide an early defense against an invading pathogen. Mast cells express an array of adhesion and immune receptors that may assist in the recognition of invading pathogens. When activated, these cells then synthesize and release key immunoregulatory cytokines, one consequence of which is to mobilize a rapid and vigorous inflammatory response. However, although it has been demonstrated that mast cells may have a role in innate immunity in defined in vitro and animal models, it remains to be determined whether mast cells are protective in innate immune responses in humans.     

巨噬细胞极化在寄生虫感染中的作用研究进展

巨噬细胞是固有免疫的重要成员,在机体防御病原生物感染、肿瘤、过敏性疾病等发生发展中发挥着极其重要的作用。巨噬细胞具有高度可塑性,在不同环境刺激下巨噬细胞可极化为经典活化型巨噬细胞（M1型巨噬细胞）和替代活化型巨噬细胞（M2型巨噬细胞）。M1型巨噬细胞能够促进机体炎症反应,有利于清除病原体;M2型巨噬细胞能够抑制炎症反应,有利于病原体生存、繁殖。本文综述巨噬细胞极化在寄生虫感染中的作用,为寄生虫病防治研究提供参考。     

Neural inhibition of inflammation: the cholinergic anti-inflammatory pathway

The innate immune system is activated by infection and injury to release pro-inflammatory cytokines, which activate macrophages and neutrophils and modulate specific cellular responses. The magnitude of the cytokine response is critical, because a deficient response may result in secondary infections, while an excessive response may be more injurious than the original insult. We recently described a neural pathway, termed the "cholinergic anti-inflammatory pathway", that reflexively monitors and adjusts the inflammatory response by inhibiting pro-inflammatory cytokine synthesis. Efferent signals in the vagus nerve provide a direct mechanism for neural regulation of the immune response that is rapid, localized, and integrated. Vagus nerve stimulation inhibits the release of TNF, HMGB1, and other cytokines, and protects against endotoxemia and ischemia-reperfusion injury. This newly identified physiological mechanism of maintaining immunological homeostasis suggests that novel therapeutics may effectively modulate inflammatory responses by activating the cholinergic anti-inflammatory pathway.     

The potential of human neutrophil peptides in tuberculosis therapy.

The problems of drug resistance and bacterial persistence in tuberculosis have prompted scientists to search for clues from the latest advances in microbiology and immunology. Recent research on human neutrophil peptides (HNPs) has highlighted their bactericidal action against Mycobacterium tuberculosis and suggested that neutrophils may play a more important defensive role in tuberculosis than previously thought. Human neutrophil peptides belong to a family of antimicrobial and cytotoxic peptides known as 'defensins'. Neutrophils use both oxidative and non-oxidative microbicidal mechanisms to provide the host with innate immunity against microbial infections. Defensins are most abundant among an array of oxygen-independent antimicrobial proteins and peptides in neutrophil granules. Defensins are effective against a wide spectrum of microbes including bacteria, viruses, fungi, spirochetes and mycobacteria. In addition to direct antimicrobial activity, HNPs can potentially influence the inflammatory or immune responses by modulating cytokine production or acting like opsonins or chemotactic factors. HNPs are active against M. tuberculosis grown in vitro or within macrophages. HNPs released by neutrophils recruited in the early lesion could attract monocytes to the site and macrophages may in vivo uptake the extracellular HNPs and kill the intracellular pathogens. As such, HNPs are potential therapeutic agents against tuberculosis. HNPs are also cytotoxic against a wide range of normal mammalian cells; however, there is evidence that defensins may not cause significant cytotoxicity at the therapeutic level. Finally, the clinical application of HNPs must be evaluated in the context of possible drug resistance, as some resistance-associated genes have been identified.     

The Roles of Neutrophils in Cytokine Storms

A cytokine storm is an abnormal discharge of soluble mediators following an inappropriate inflammatory response that leads to immunopathological events. Cytokine storms can occur after severe infections as well as in non-infectious situations where inflammatory cytokine responses are initiated, then exaggerated, but fail to return to homeostasis. Neutrophils, macrophages, mast cells, and natural killer cells are among the innate leukocytes that contribute to the pathogenesis of cytokine storms. Neutrophils participate as mediators of inflammation and have roles in promoting homeostatic conditions following pathological inflammation. This review highlights the advances in understanding the mechanisms governing neutrophilic inflammation against viral and bacterial pathogens, in cancers, and in autoimmune diseases, and how neutrophils could influence the development of cytokine storm syndromes. Evidence for the destructive potential of neutrophils in their capacity to contribute to the onset of cytokine storm syndromes is presented across a multitude of clinical scenarios. Further, a variety of potential therapeutic strategies that target neutrophils are discussed in the context of suppressing multiple inflammatory conditions.     

Strategic targets of essential host-pathogen interactions

This review summarizes the present concepts regarding the biological processes that mediate intrinsic and innate host defense against microbial invasion of the lung. Innate immunity is the first line of defense of the higher organisms towards invading pathogens. It accomplishes a wide variety of activities including recognition and effector functions. The innate responses use phagocytic cells (macrophages, monocytes, and neutrophils), cells that release inflammatory mediators (basophils, mast cells, and eosinophils), and natural killer cells. The molecular component of innate responses includes complement, acute-phase proteins, and cytokines. Recognition of pathogen-associated molecular patterns is mediated by the pathogen receptors of the innate immune system, among these molecules toll-like receptors have emerged as fundamental components in the innate immune responses to infection, and a link between innate and adaptive immunity. Additional protection comes from polypeptide mediators of the innate host defense, such as the defensins and other antibiotic peptides. In view of the considerable burden in terms of mortality and morbidity that severe infections still pose worldwide, a better understanding of the biological basis of host-pathogen interactions opens stimulating future treatment perspectives.     

Intestinal dendritic cells in the pathogenesis of inflammatory bowel disease

The gastrointestinal tract harbors a large number and diverse array of commensal bacteria and is an important entry site for pathogens.For these reasons,the intestinal immune system is uniquely dedicated to protect against infections,while avoiding the development of destructive inflammatory responses to the microbiota.Several models have been proposed to explain how the immune system discriminates between,and appropriately responds to,commensal and pathogenic microorganisms.Dendritic cells(DCs)and regulato...     

The investigations of the role of toll-like receptors (TLR) in host response to parasitic infection on the current background regarding TLR in mammals and the model nematode Caenorhabditis elegans

Toll-like receptors (TLRs) are amongst the most highly conserved in the evolution of receptor family, being found in both immune and other cells. TLRs were observed in vascular endothelial cells, epithelial cells, microglia cells, adipocytes, and intestinal and renal cells. TLRs plays a key role in the innate immune response to a variety of pathogens. At present, very little is known about the role of TLRs in host defense against parasitic pathogen infections. The first study shows that TLRs contribute to both innate and adaptive immune responses following infection with protozoan parasite Leishmania major. The TLRs recognizing PAMPs associated with the parasite L. major are essential for the activation of the innate and adaptive immune responses to infection. A study concerning recognition of the role of TLRs in the host-parasite relationship would be an interesting challenge for future study.     

Allergy and immunity to fungal infections and colonization.

Innate and cell-mediated immunity are considered as the principal defence lines against fungal infections in humans. Most opportunistic mycoses occur in individuals with defective innate and/or adaptive cellular immunity. The morbidity and mortality rates associated with infections caused by fungal pathogens are high, and prevention, diagnosis and treatment of these infections remain quite difficult. A variety of pathological conditions, including impaired immune function, are believed to cause host susceptibility to fungal infections as well as to determine the severity and characteristics of the associated pathology. Nonspecific cellular immunity, mediated by macrophages, neutrophils and natural killer cells, provides efficient protection against fungal infections in healthy individuals. A major reason for the increase in systemic mycoses is undoubtedly related to an increased number of patients with congenital or acquired immunodeficiencies. However, there is increasing clinical and experimental evidence indicating that antigen-specific cellular immunity may also play a critical role in host protection against fungi. A better understanding of reciprocal regulation between innate, humoral and adaptive immune responses in the development of an optimal antifungal immunity and, in particular, the improved definition of fungal antigens, may lead to a clarification of the mechanisms involved in host immunity to fungal infections. Molecular cloning and characterization of fungal antigens reveals the involvement of related cross-reactive molecular structures produced by different fungi as pathological molecules involved in development of allergic reactions.     

Genetic immunization in the lung induces potent local and systemic immune responses

Successful vaccination against respiratory infections requires elicitation of high levels of potent and durable humoral and cellular responses in the lower airways. To accomplish this goal, we used a fine aerosol that targets the entire lung surface through normal respiration to deliver replication-incompetent recombinant adenoviral vectors expressing gene products from several infectious pathogens. We show that this regimen induced remarkably high and stable lung T-cell responses in nonhuman primates and that it also generated systemic and respiratory tract humoral responses of both IgA and IgG isotypes. Moreover, strong immunogenicity was achieved even in animals with preexisting antiadenoviral immunity, overcoming a critical hurdle to the use of these vectors in humans, who commonly are immune to adenoviruses. The immunogenicity profile elicited with this regimen, which is distinct from either intramuscular or intranasal delivery, has highly desirable properties for protection against respiratory pathogens. We show that it can be used repeatedly to generate mucosal humoral, CD4, and CD8 T-cell responses and as such may be applicable to other mucosally transmitted pathogens such as HIV. Indeed, in a lethal challenge model, we show that aerosolized recombinant adenoviral immunization completely protects ferrets against H5N1 highly pathogenic avian influenza virus. Thus, genetic immunization in the lung offers a powerful platform approach to generating protective immune responses against respiratory pathogens.