Chemokines and Chemokine Receptors in the Central Nervous System: New Opportunities for Novel Therapeutics in Brain Ischemia and Trauma

Abstract

The superfamily of chemokines (chemoattractant cytokines) consists of a broad array of polypeptides of diverse biological actions and structures (Fig. l).The current number of chemokines exceeds 50 related proteins. These proteins range in size from 68–120 amino acids (in the mature form) and can be segregated into at least four structural branches: C, C-C, C-X-C, and CXXXC according to variations in a shared cysteine motif. The largest branch, i.e., the C-C or β-chemokines, has nearly twenty members in humans while the smallest branch, the C class, has only one (Oppenheim et al. 1991; Rollins 1997; Mantovani 1999; Kelner et al. 1994; Pan et al. 1997). The C-X-C, or the β-chemokine branch can be further subdivided by structure and function into proteins containing the amino acid motif E-L-R-C-X-C (the majority) and those few that do not have the E-L-R motif adjunct to C-X-C. Structural distinctions of the different branches of the superfamily of chemokines have been shown to parallel general (though not absolute) distinctions in their biological activities (Fig. 2). For example, most C-X-C chemokines (those with E-L-R) are chemoattractants for neutrophils but not for monocytes, whereas C-C chemokines generally attract monocytes and lymphocytes, but not neutrophils. Basophils and eosinophils are also affected by C-C chemokines. The C chemokine appears thus far to be lymphocyte-specific.