By Robert M. Strieter, Steven L. Kunkel, Theodore Standiford
Discusses the position of chemokines in mediating leukocyte trafficking, angiogenesis, tumor cellphone metastasis, host safety, trauma-induced lung harm, and the development of AIDS within the lung. experiences cytokines as normal brokers for modulating ailments that impact the lung
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11. Kawabata K, Ujikawa M, Egawa T, Kawamoto H, Tachibana K, Iizasa H, Katsura Y, Kishimoto T, Nagasawa T. A cell-autonomous requirement for CXCR4 in longterm lymphoid and myeloid reconstitution. Proc Natl Acad Sci USA 1999; 96:5663– 5667. 12. Yoshida T, Imai T, Takagi S, Nishimura M, Ishikawa I, Yaoi T, Yoshie O. Structure and expression of two highly related genes encoding SCM-1/human lymphotactin. FEBS Lett 1996; 395:82–88. 13. Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A.
In this model, binding of chemokine to receptor promotes tyrosine phosphorylation of the receptor and association of JAK to the receptor, which then recruits STAT into a signaling complex, thereby activating STAT-dependent gene transcription. Since both JAK association and receptor tyrosine phosphorylation occur even in the presence of PTX, JAK activation may be upstream of or parallel to Gi activation (26–28). Whether this model can be generalized to all chemokine receptors is unknown, and its relevance to CCR2 function in vivo is not yet established.
In contact hypersensitivity studies, CCR6Ϫ/Ϫ mice developed more severe and more persistent inflammation, whereas in a delayedtype hypersensitivity model, CCR6Ϫ/Ϫ mice have no inflammatory response, suggesting that CCR6 is also involved in the activation or migration of CD4ϩ T-cell subsets that down-regulate or elicit the inflammatory response (83). Chemokine Receptors: Mechanisms and Roles 23 2. CCR2 CCR2 also plays a role in DC trafficking in vivo. In CCR2-knockout mice, Langerhans cell density is normal, and migration of Langerhans cells to dermis is intact.
