ABSTRACT
Chemokines (chemotactic cytokines) are small soluble proteins of 68 to 127 amino acids with four conserved cysteines linked by disulfide bonds. The two main subfamilies, CXC and CC chemokines, are defined on the basis of the first two cysteines which are separated by one amino acid or are adjacent [1-5]. The inducible CXC and CC chemokines also differ in the chromosomal localization of their genes which are on human chromosome 4 and 17, respectively. No similar clustering of the genes for homing chemokines is seen. Currently, the family of human chemokines consists of more than 40 proteins, and the nomenclature of those with known receptor selectivity is presented in Table I. With a few exceptions, inducible chemokines act on more than one type of leukocyte, and their main function is the recruitment of effector cells to the site of
inflammation and immune responses [1-5]. Additional responses of monocytes, granulocytes and lymphocytes include enzyme release from intracellular stores, oxygen radical formation, shape change through cytoskeletal rearrangement, generation of lipid mediators, and induction of adhesion to endothelial or extracellular matrix proteins. Some chemokines stimulate blood progenitor cells. The apparent overlap in target cell selectivity and repertoire of cellular responses can be taken as a measure for the critical importance of chemokines in the regulation of defensive mechanisms in disease. Chemokine production is rapidly induced in a variety of blood and tissue cells upon stimulation with proinflammatory cytokines (TNFα, IL-1, IFN-γ), lipopolysaccharide, phorbol esters or other stimuli while constitutive expression is generally low [1,2]. By contrast, many tumors and leukemia cells generate chemokines without prior stimulation.
