The chemokine Cxcl12 binds Cxcr4 and Cxcr7 receptors to control cell migration in multiple biological contexts, including brain development, leukocyte trafficking, and tumorigenesis. Both receptors are expressed in the CNS, but how they cooperate during migration has not been elucidated. Here, we used the migration of cortical interneurons as a model to study this process. We found that Cxcr4 a...

Chemokines mediate trafficking of leukocytes to sites of inflammation and immune responses through activation of G protein-coupled receptors, which thereby provide appealing targets for novel anti-inflammatory agents. Vasoactive intestinal peptide (VIP) is an immunosuppressive neurotransmitter. We show that VIP inhibited the function of chemokine receptors on monocytes and CD4(+) T lymphocytes,...

Many HIV-1-positive individuals suffer from a variety of neurological problems known collectively as the HIV-1-related cognitive-motor complex. However, the molecular mechanisms that underlie HIV-1-induced neuropathology are unclear. They might include a combination of indirect effects, which result from the release of neurotoxins from activated astrocytes and microglia, and the direct effects ...

Chemokine and chemokine receptors show several variations which may affect resistance to infectious disease. A 32 base pair deletion in the open reading frame of the human CCR5 gene (CCR5?32) results in producing a truncated antigen which fails to be presented on the surface of target cells. CCR5?32 variant is not a functional co receptor for HIV-1 entrance and delay the onset of acquired immun...

Infiltration of renal allografts by leukocytes is a hallmark of acute transplant rejection. Chemokines attract leukocytes bearing specific chemokine receptors, and the specific leukocyte chemokine receptor phenotype is associated with types of immune responses, ie, T helper subtype 1 (Th1; CXC chemokine receptor 3 [CXCR3], CC chemokine receptor 5 [CCR5]) versus Th2 (CCR3, CCR4, CCR8). We studie...

Chemokine receptors belong to the superfamily of G protein-coupled receptors, which regulate the trafficking and activation of leukocytes, and operate as coreceptors in the entry of HIV-1. To investigate the early steps in the signal transmission from the chemokine-binding site to the G protein-coupling region we engineered metal ion-binding sites at putative extracellular sites in the chemokin...

Recruitment of inflammatory cells to vascularised allografts is a hallmark of rejection, and paves the way for chronic allograft injury. Chemokines play pivotal roles in the directed movement of leukocytes. Herein, we define the distribution of chemokine receptors for the most common cell types during human lung allograft rejection as a prerequisite for therapeutic interventions. Immunohistoche...

Other than signalling receptors sustaining leucocyte recruitment during inflammatory reactions, the chemokine system includes 'silent' receptors with distinct specificity and tissue distribution. The best-characterized molecule of this subgroup is the CC chemokine receptor D6, which binds most inflammatory CC chemokines and targets them to degradation via constitutive ligand-independent interna...

In the search for new treatments for human inflammatory disease, antagonism of chemokine receptors by small molecules is an attractive goal. Although there are overlapping patterns of expression of chemokine receptors between leucocyte types, an investigation of the chemokine responsiveness of cells important in allergic inflammation, such as the eosinophil and the basophil, is beginning to unc...