By Robert M. Strieter, Steven L. Kunkel, Theodore Standiford
Discusses the position of chemokines in mediating leukocyte trafficking, angiogenesis, tumor telephone metastasis, host protection, trauma-induced lung harm, and the development of AIDS within the lung. reports cytokines as typical brokers for modulating ailments that have an effect on the lung
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Extra info for Chemokines in the Lung
Importantly, the chemokine superfamily is among the ﬁrst molecular superfamilies for which all members are known, at least in the human. This has been achieved by producing databases of expressed sequence tags (EST) of transcripts expressed by a variety of cells and tissues of the body. The most comprehensive databases were produced initially for the human. The chemokines were ideal proteins to discover in this way, largely because these molecules exhibit two unique characteristics: ﬁrst, they are produced in very large amounts by those cells that produce them; and second, most chemokines are small peptides that contain a characteristic sequence, namely four cysteines in conserved positions.
After exposure to inﬂammatory mediators, such as tumor necrosis factor (TNF)-α, IL-1, lipopolysaccharides (LPS), or other signals delivered by the innate immune system, DCs transform into mature DCs and migrate to lymphoid organs. This process is regulated by chemokines and chemokine receptors (see Chap. 4 for additional discussion). Immature DCs express “inﬂammatory” chemokine receptors, such as CCR1, CCR2, CCR5, CXCR2, and CCR6, whereas mature DCs down-regulate “inﬂammatory” receptors and up-regulate the key “lymphoid” or “homeostatic” chemokine receptor CCR7.
Interspecies Chemokine Homology: Therapeutic Implications Further analysis of Table 1 illustrates the fact that some chemokine ligands lack functional and structural similarity between species. Lungkine/CXCL15 is found uniquely in the mouse, whereas IL-8/CXCL8 and CCL18 exist only in the human. Importantly, the MCP subfamily includes four chemokines in humans and four in the mouse, although it is virtually impossible to ascribe with certainty which mouse molecule corresponds to which human ligand.