Chemokines, their Receptors and Significance in Brain Function

Abstract

Chemo-attractant cytokines, now known as chemokines, comprise the largest and most diverse subset of cytokines identified to date. Chemokines are characterized by their capacity to bring about the directional migration and activation of leucocytes and other somatic cell types during inflammation; cell-mediated immune reactions; to regulate cell adhesion, angiogenesis, leukocyte trafficking and homing, as well as lymphopoiesis and hematopoiesis. Chemokines are produced by a wide variety of leukocytes and other cell types in response to inflammatory agents, antigens, and endogenous cytokines. Studies of the in vivo effects of neutralizing antibodies and homologous deletions of chemokine genes reveal that chemokines play a central role in host defense against infectious organisms. Chemochines are relevant in normal central nervous system (CNS) physiology and development, as well as in the pathogenesis of diverse conditions such as tumor metastasis, riperfusion injuries and stroke. Chemokine structure, expression in CNS, and systematic classification schemes are presented according to (1) their constitutive expression and (2) their inducibility in response to inflammatory stimuli. The classification of chemokine receptor expression in specific CNS cells and their principal intracellular signal transduction pathways are also included, in addition to their various physiological roles. Consideration is given to the fascinating hypothesis that chemokines may influence neural and glial cell migration and proliferation during CNS development. The immuno-competence of the CNS, including inflammatory cell recruitment into the CNS as a function of chemokines in the evolution of pathological and host defense processes, is explored for head trauma, brain ischemia and trauma, AIDS dementia, Alzheimer’s disease, and brain tumor progression.