Chapter 26 - Chemokines

Abstract

Chemokines have multiple roles in the organization of the immune system under basal conditions and during infection, and are also involved in angiogenesis. A crucial role of chemokines is the recruitment of different types of leukocytes from the blood to the sites of inflammation. Most of the known chemokines belong to two major families defined by the position of four conserved cysteine residues. The largest family is the CC chemokine family (28 in number), which possesses two adjacent cysteines in the vicinity of the N-terminus of the mature peptide. The CXC family (16 members) has two cysteine residues in this same region, but with an interposed amino acid. Chemokines are thought to bind to presenting molecules on the luminal surface of the venular endothelium, such as glycosaminoglycans, where the chemokines engage their receptors on the leukocyte surface. A combination of clinical observations, in vitro cell biology and in vivo animal modeling has delineated potentially important mechanisms underlying lung inflammation in COPD and asthma. These extensive studies support the hypothesis that chemokines have a fundamental role in regulating leukocyte trafficking in inflammatory disease. The chemokine receptors represent novel targets for treatment and therapeutic compounds have been described with efficacy in vitro and in vivo.