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IL-8 receptor antagonist: basic research and clinical utility

  • John R. White
  • Henry M. Sarau
Part of the Progress in Inflammation Research book series (PIR)

Abstract

Inflammatory cells are thought to be instrumental in the pathophysiology of diseases and the control of their recruitment and activation appears to be an attractive strategy for therapeutic intervention. Chemokines are a family of small molecular weight (7–15 kDa) proteins that in conjunction with adhesion molecules play a crucial role in leukocyte recruitment, cellular activation and proliferation at sites of inflammation. Chemokines are produced by a variety of cell types, including leukocytic and non-leukocytic cells, usually in response to antigens, irritants and other cytokines. Interleukin-8 (CXCL8) was the first member to be identified of this new family of proinflammatory chemokines that now constitute over 45 members. Chemokines produce their biological effects by interacting with greater than 18 G protein coupled cell surface receptors. A few chemokines bind selectively to a single receptor but other chemokines bind to more than one receptor [1, 2]. CXCL8 belongs to a subgroup of chemokines known as ELR+ chemokines because of the Glu4-Leu5-Arg6 amino acid sequence between positions 4 and 6. Other members of this group include CXCL1, 2, 3, 5, 6, and 7. A diverse variety of biological effects are attributed to CXCL8 and related ELR+ chemokines, including several involving inflammatory cell activation and chemotaxis, production of reactive oxygen species, increased expression of the integrin CD11b-CD18, enhancement of cell adhesion to endothelial cells, promotion of angiogenesis, modulation of histamine and lipid mediator release as well as azurophil granule release [3].

Keywords

Chronic Obstructive Pulmonary Disease Chronic Obstructive Pulmonary Disease Patient Respir Crit CXCR2 Antagonist Chronic Obstructive Pulmonary Disease Lung 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag Basel/Switzerland 2007

Authors and Affiliations

  • John R. White
    • 1
  • Henry M. Sarau
    • 2
  1. 1.Biopharmaceutical CEDDGlaxoSmithKlineKing of PrussiaUSA
  2. 2.Respiratory and Inflammation CEDDGlaxoSmithKlineKing of PrussiaUSA

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