AP183P Sigma-AldrichGoat Anti-Rat IgG Antibody, HRP conjugate, Species Adsorbed

Na(x) is an atypical sodium channel that is assumed to be a descendant of the voltage-gated sodium channel family. Our recent studies on the Na(x)-gene-targeting mouse revealed that Na(x) channel is localized to the circumventricular organs (CVOs), the central loci for the salt and water homeostasis in mammals, where the Na(x) channel serves as a sodium-level sensor of the body fluid. To understand the cellular mechanism by which the information sensed by Na(x) channels is transferred to the activity of the organs, we dissected the subcellular localization of Na(x) in the present study. Double-immunostaining and immunoelectron microscopic analyses revealed that Na(x) is exclusively localized to perineuronal lamellate processes extended from ependymal cells and astrocytes in the organs. In addition, glial cells isolated from the subfornical organ, one of the CVOs, were sensitive to an increase in the extracellular sodium level, as analyzed by an ion-imaging method. These results suggest that glial cells bearing the Na(x) channel are the first to sense a physiological increase in the level of sodium in the body fluid, and they regulate the neural activity of the CVOs by enveloping neurons. Close communication between inexcitable glial cells and excitable neural cells thus appears to be the basis of the central control of the salt homeostasis.

Macrophage mannose receptor (MMR) is an important component of the innate immune system implicated in host defense against microbial infections such as candidiasis and in antigen presentation. We demonstrate here that the MMR expression is induced in mouse peritoneal macrophages following exposure to PPARgamma ligands or to interleukine-13 (IL-13) via a PPARgamma signaling pathway. Ligand activation of the PPARgamma in macrophages promotes uptake, killing of Candida albicans, and reactive oxygen intermediates production triggered by the yeasts through MMR overexpression. We also show that MMR induction by IL-13 via PPARgamma is dependent on phopholipase A2 activation and that IL-13 induces 15d-PGJ2 production and nuclear localization. These results reveal a novel signaling pathway controlling the MMR surface expression and suggest that endogenous PPARgamma ligand produced by phospholipase A2 activation may be an important regulator of MMR expression by IL-13.

Epithelioid cells (ECs) found in granulomas are thought to derive from mononuclear phagocytes. Although GM-CSF and/or IL-4 are known to promote cell differentiation their role in the development of ECs has never been demonstrated. Here we showed that mouse macrophages treated exclusively with recombinant IL-4 (rIL-4) differentiate into epithelioid-like cells. Macrophages cultivated with rIL-4 presented a fried-egg shape, and ultrastructural studies revealed membrane interdigitations, cytoplasmic vesicles, prominent Golgi complex, and rough endoplasmic reticulum. Compared with controls, rIL-4 treated cells displayed increased expression of MHC class II molecules and of Migration Inhibitory Factor-Related Protein-14. Whereas mannose receptor-mediated phagocytosis was increased, Fcgamma-receptor mediated phagocytosis and the production of nitric oxide were decreased in treated cultures. All these features overlap those reported for ECs from granulomatous lesions. In conclusion, treatment of mouse peritoneal macrophages with rIL-4 drives their in vitro differentiation to an epithelioid phenotype and provides a tool to investigate the biology of ECs.