Chemokines

Inflammation Research -     

Chemokines

Chemokines are small proteins that control cellular migration. An extensive family of these molecules has been described in mammals containing nearly 50 members. Within this family are four groups, each defined by the different spacing of two N-terminal cysteines, which form disulphide bonds with two other cysteine residues to create the tertiary structure characteristic of chemokines. Recent evidence shows the chemokine family is not unique to mammals, with several members also identified in birds, amphibians and fish, including a primitive vertebrate, the lamprey. Although there is less evidence to define the roles of chemokines in these lower vertebrates, structural similarities allow some predictions to their function, against which further studies are being made. Additionally, some microorganisms (particularly viruses) appear to have copied genes for chemokines, presumably to confuse the immune system of their host. This review aims to bring together the current information concerning identified chemokines throughout vertebrates and microorganisms.     

Chemokines and disease

We examine here several diseases that are associated with inappropriate activation of the chemokine network. Detailed comment has been restricted to pathological states for which there are compelling data either from clinical observations or animal models. These include cardiovascular disease, allergic inflammatory disease, transplantation, neuroinflammation, cancer and HIV-associated disease. Discussion focuses on therapeutic directions in which the rapidly evolving chemokine field appears to be headed.     

Chemokines in allergy

Knowledge of the chemokine superfamily has undergone a dramatic expansion during the past decade. Currently, we are witnessing a transition from a phase of molecular discovery to a phase of disease associations and the establishment of functional (clinical) relevance. Recent data regarding the expression of chemokines and their receptors in pathologically relevant cells as well as observations using gene-targeting approaches have given us a better understanding of the complex mechanisms involved in leukocyte recruitment and inflammation as well as their potential role in the immunopathogenesis of human diseases.     

趋化因子与免疫调节性细胞因子

趋化因子与免疫调节性细胞因子的生物学功能是目前生物学的研究热点之一。不同的免疫调节性细胞表达不同的趋化因子受体，受不同趋化因子的作用而分泌不同的免疫调节性细胞因子。深入研究它们之间的相互关系，通过调控它们表达，进而达到控制和治疗疾病的目的。     

Lymphocyte Responses to Chemokines

Today, almost three dozen human chemokines have been identified. The main function of these soluble proteins is the recruitment of leukocytes to sites of infection and inflammation. This review emphasizes the new developments in the field of lymphocyte responses to chemokines. Notably, it was shown that lymphocytes require stimulation to become responsive to chemokines, a process that is closely linked to chemokine receptor expression. As an exception, one chemokine, SDF-1, is a highly effective chemoattractant for non-activated T lymphocytes and progenitor B cells. Of particular interest are the chemokines IP10 and Mlg which bind to a receptor with selective expression in activated T lymphocytes and, therefore, may be critical mediators of T lymphocyte migration in T cell-dependent immune-responses. All other chemokines with activities in lymphocytes do also induce responses in monocytes and granulocytes. The involvement of chemokine receptors in HIV infection is briefly mentioned, while other interesting areas in chemokine research, such as hematopoiesis and angiogenesis, are not discussed.     

Chemokines and leukocyte traffic

Twenty years after the discovery of chemokines is an appropriate time to review leukocyte traffic and to assess the knowledge and opportunities that have arisen from countless studies of the large and tight-knit family of chemotactic proteins.     

Chemokines in autoimmune disease

Growing evidence indicates that structural cells play a crucial role in the chronic inflammation of autoimmunity by their recruitment of chemokine-dependent cells. Members of the two functional classes of chemokines, inflammatory and homeostatic, seem to be involved in lymphocyte recruitment and survival, and in establishing ectopic lymphoid structures in the target organs of autoimmune diseases. Results from animal models suggest that chemokines are reasonable therapeutic targets in autoimmunity.     

Posters: Chemokines 1

Inflammation Research -     

Chemokines and innate immunity

Our environment contains a great variety of infectious microbes that may be potentially destructive and threaten our survival. As soon as microbes try to establish a site of infection, the host launches a complex defense system. Innate immunity is a non-specific response and serves as the first-line of defense where phagocytes, such as neutrophils and macrophages, and NK cells play central roles in neutralizing and clearing microorganisms. Thus, migration of cells into infectious foci and subsequent activation of these cells appear to be a critical step, enabling the host to achieve effective and efficient removal of microbes. Over the past decade, chemokines have been identified as chemotactic cytokines that attract and activate specific types of leukocyte populations in vitro. There is now evidence that the magnitude of chemokines' expression in infectious diseases is strongly associated with the severity of the inflammatory responses. Blocking chemokines or their receptors with neutralizing antibodies or gene targeting technology has allowed us to understand the pathological significance of chemokines in animal models of infectious diseases. Growing evidence suggests that chemokines play an important beneficial role in immune system development, homeostasis and in innate immunity, which may pave the way for new therapeutic strategies for the treatment of infectious diseases.     

趋化因子与树突状细胞

树突状细胞(DC)是骨髓来源的专职抗原呈递细胞。DC可引起T细胞活化和耐受从而启动和抑制免疫反应。DC居留在所有组织和器官,在活化后可移动到周围淋巴器官,呈递抗原至T区的T细胞。由于DC在T细胞活化中的中心作用,在治疗学上利用DC对免疫系统递送阳性和阴性信号引发广泛兴趣。不同成熟阶段的DC,与趋化因子之间相互作用。该综述主要描述DC与趋化因子的交互作用。