Scavenging roles of chemokine receptors: chemokine receptor deficiency is associated with increased levels of ligand in circulation and tissues
Creator
Cardona A E; Sasse M E; Liu L P; Cardona S M; Mizutani M; Savarin C; Hu T; Ransohoff R M
Publisher
Blood
Date
2008
2008-07
Description
In vitro studies have implicated chemokine receptors in consumption and clearance of specific ligands. We studied the role that various signaling chemokine receptors play during ligand homeostasis in vivo. We examined the levels of ligands in serum and CNS tissue in mice lacking chemokine receptors. Compared with receptor-sufficient controls, Cx3cr1(-/-) mice exhibited augmented levels of CX3CL1 both in serum and brain, and circulating levels of CXCL1 and CXCL2 were increased in Cxcr2(-/-) mice. CCR2-deficient mice showed significantly increased amounts of circulating CCL2 compared with wild-type mice. Cxcr3(-/-) mice revealed increased levels of circulating and brain CXCL10 after experimental autoimmune encephalomyelitis (EAE) induction. CCR2-deficient peripheral blood and resident peritoneal cells exhibited reduced binding capacity and biologic responses to the CCR1 ligand CCL3, suggesting that elevated levels of CCR2 ligands had down-regulated CCR1. The results indicate that signaling chemokine receptors clear chemokines from circulation and tissues. These homeostatic functions of signaling chemokine receptors need to be integrated into safety and efficacy calculations when considering therapeutic receptor blockade.
Auditory nerve fiber differences in the normal and neurofilament deficient Japanese quail.
Creator
Sheykholeslami K; Kaga K; Mizutani M
Publisher
Hearing research
Date
2001
2001-09
Description
A primary axonal disease affecting the central and peripheral nervous system was discovered in a mutant strain of the Japanese quail, named quiver (Quv). We have previously demonstrated altered auditory evoked potentials in the neurofilament (NF) deficient quail. In this current study we attempt to find relationships between the auditory evoked potential results and the histo-pathological abnormalities of the auditory neurons. No abnormalities in the external auditory meatus and tympanic cavity were observed in either Quv or control quails and the ganglion cell bodies and their nuclei appeared normal by light microscopy. The myelin staining pattern was found to be similar in both strains with hematoxylin and eosin and Kluver-Barrera staining. The frequency histograms of fiber and axonal diameters of myelinated fibers showed an unimodal pattern in both strains. In Quv quails myelinated fibers and their axoplasm were smaller in diameter than in controls resulting in smaller neural tissue mass. In electron microscopic observation the axons of the Quv quail were composed of mitochondria and microtubules and smooth endoplasmic reticuli. In Quv quail electron micrographs of cochlear nerve myelinated fibers NFs were not seen in the axons and the neuronal cell bodies. Our current findings indicate that the previously reported reduction of conduction velocity of auditory evoked potentials may be due to smaller fiber and/or axonal diameter. The g-ratio, myelin thickness and fiber circularity were found to be the same for both strains. In conclusion, loss of axonal cytoskeletal elements (NFs) correlates well with our electrophysiological findings. Reduced conduction velocity and severely distorted auditory evoked potentials in NF deficient quails seem to be primarily due to axonal hypotrophy.