Orphan chemokine receptors in neuroimmunology: functional and pharmacological analysis of L-CCR and HCR

In this thesis we have investigated the expression and biological activity of the orphan chemokine receptors L-CCR/HCR in astrocytes and microglia. Several lines of evidence indicate that the chemokines CCL2, CCL5, CCL7 and CCL8 are agonists for these receptors. Although a variety of biological L-CCR/HCR responses have been found, high affinity radioligand binding with CCL2 and CCL5 was not observed. Accordingly, an official classification of these receptors is not yet possible. Moreover, the results presented strongly indicate a role expression of L-CCR/HCR in neuroinflammation. L-CCR/HCR expression might explain the effects of CCL2 in astro-cytes lacking the classical CCL2 receptor. More information on the importance of L-CCR/HCR in neuroinflammation and particularly their role in astrocytes should be obtained in L-CCR deficient mice.