ABSTRACT
A inflamação é parte do processo fisiológico que visa reparar o dano tecidual causado por infecção, trauma, auto-imunidade. Quando este processo fisiológico encontra-se alterado, pode contribuir para o aumento do dano tecidual. As quimiocinas e seus receptores são importantes elementos envolvidos no processo de migração celular para os tecidos inflamados. Nas doenças oculares, principalmente nas uveítes, estas proteínas estão sendo identificadas como importantes mediadores da resposta inflamatória. Esta revisão visa discutir o papel das quimiocinas em diversas doenças oculares, dando ênfase aos processos uveíticos.
Inflammation is part of the physiological process that aims at repairing the damage produced by different causes such as infection, trauma, and autoimmune disease. However, when this physiological process is not regulated, it can contribute to the increase in tissue damage. Chemokines and their receptors are major factors involved in the process of cell migration into inflamed tissues. In the ocular diseases, mainly in uveitis, such proteins have been identified as important mediators of the inflammation process. This review discusses the role of chemokines in several ocular diseases, with emphasis on the uveitic process.
Subject(s)
Humans , Chemokines/physiology , Uveitis/physiopathology , Inflammation Mediators , Receptors, Chemokine/physiologyABSTRACT
Inflamação é parte do processo fisiológico que visa reparar o dano tecidual causado por infecção, trauma, isquemia, autoimunidade. Entretanto, quando o processo inflamatório não é controlado, pode contribuir para o aumento da lesão tecidual. A regulação da resposta inflamatória no sistema nervoso central (SNC) envolve diferentes tipos celulares, como neutrófilos, macrófagos e linfócitos, células da glia, moléculas de adesão, citocinas e quimiocinas. As quimiocinas são uma família de citocinas de baixo peso molecular responsáveis pelo recrutamento seletivo de leucócitos, e subdividem-se em quatro subfamílias de acordo com a posição do resíduo cisteína N-terminal dessas moléculas: C, CC, CXC, CX3C. O objetivo desta revisão é apresentar o papel das quimiocinas na regulação da inflamação em doenças do SNC.
Inflammation is part of the physiological process that aims at repairing the tissue damage produced by infection, trauma, ischemia, autoimmune diseases. However, when this process is not controlled, it can increase the tissue lesion. The regulation of the inflammatory response in the central nervous system (CNS) involves different cell types such as neutrophils, macrophages, lymphocytes, glia cells, adhesion molecules, cytokines and chemokines. Chemokines are a large family of low-molecular weight cytokines associated with the selective trafficking of leukocytes, and are classified into four subfamilies on the basis of the arrangement of cysteine residues located in the N-terminal region of these molecules: C, CC, CXC and CX3C. This review will attempt to describe the role of chemokines in the regulation of inflammation in CNS diseases.
Subject(s)
Central Nervous System Diseases/physiopathology , Inflammation/physiopathology , Inflammation/immunology , Leukocytes/immunology , Leukocytes/metabolism , Chemokines/physiology , Receptors, Chemokine/physiologyABSTRACT
Chemokine receptors are G protein-coupled receptors that mediate migration and activation of leukocytes as an important part of a protective immune response to injury and infection. In addition, chemokine receptors are used by HIV-1 to infect CD4 positive cells. The structural bases of chemokine receptor recognition and signal transduction are currently being investigated. High-resolution X-ray diffraction and NMR spectroscopy of chemokines indicate that all these peptides exhibit a common folding pattern, in spite of its low degree of primary-sequence homology. Chemokines' functional motifs have been identified by mutagenesis studies, and a possible mechanism for receptor recognition and activation is proposed, but high-resolution structure data of chemokine receptors is not yet available. Studies with receptor chimeras have identified the putative extracellular domains as the major selectivity determinants. Single-amino acid substitutions in the extracellular domains produce profound changes in receptor specificity, suggesting that motifs in these domains operate as a restrictive barrier to a common activation motif. Similarly HIV-1 usage of chemokine receptors involves interaction of one or more extracellular domains of the receptor with conserved and variable domains on the viral envelope protein gp 120, indicating a highly complex interaction. Elucidating the structural requirements for receptor interaction with chemokines and with HIV-1 will provide important insights into understanding the mechanisms of chemokine recognition and receptor activation. In addition, this information can greatly facilitate the design of effective inmunomodulatory and anti-HIV-1 therapeutic agents
Subject(s)
Humans , CD4-Positive T-Lymphocytes/virology , HIV/metabolism , Receptors, Chemokine/chemistry , Receptors, Chemokine/physiology , Receptors, Chemokine/metabolism , Receptors, HIV/metabolismABSTRACT
The selective recruitment of eosinophils in tissue is a striking feature of allergic diseases. Recently, a family of chemoattractant molecules, namely chemokines, has been described which potently activates eosinophil function in vitro. We have developed a murine model of eosinophil recruitment to compare the relative potency and efficacy of chemokines in vivo. Of the chemokines tested, only eotaxin and MIP-1alpha induced significant accumulation of eosinophils in vivo, but eotaxin was more effective than MIP-1alpha. Chemokines, especially eotaxin acting via the CCR-3 receptor, may have a fundamental role in determining selective eosinophil recruitment in vivo.
Subject(s)
Mice , Animals , Chemokines/physiology , Eosinophils/physiology , Receptors, Chemokine/physiologyABSTRACT
El reciente descubrimiento de dos nuevos co-receptores utiliados por el HIV-1 para la penetración de células blanco permite una mejor comprensión de los mecanismos de interacción virus-huésped. El concomitante descubrimiento de que estos receptores son utilizados por quimiokinas allana aún más el camino en la interpretación de la biología molecular y la fisiopatología de la infección por HIV. Estos hallazgos permiten planear nuevas estrategias terapéuticas destinadas a bloquear la interacción virus-receptor.