CXCL12a/CXCR4b acts to retain neutrophils in caudal hematopoietic tissue and to antagonize recruitment to an injury site in the zebrafish larva.

Neutrophils are a major component of the innate immune response and the most abundant circulating cell type in humans and zebrafish. The CXCL12/CXCR4 ligand receptor pair plays a key role in neutrophil homeostasis, controlling definitive hematopoiesis and neutrophil release into circulation. Neutrophils overexpressing CXCR4 respond by migrating towards sources of CXCL12, which is abundant in hematopoietic tissues. However, the physiological role of CXCL12/CXCR4 signaling during inflammatory responses remains unknown. Here, we show that zebrafish mutants lacking functional CXCL12a or CXCR4b show disrupted granulopoiesis in the kidney and increased number of circulating neutrophils. Additionally, CXCL12a and CXCR4b mutants display exacerbated recruitment of neutrophils to wounds and not to infections, and migrating neutrophils to wounds show increased directionality. Our results show that CXCL12a/CXCR4b signaling antagonizes wound-induced inflammatory signals by retaining neutrophils in hematopoietic tissues as a part of a balance between both inflammatory and anti-inflammatory cues, whose dynamic levels control neutrophils complex migratory behavior.

Bone morphogenetic protein 2 inhibits neurite outgrowth of motor neuron-like NSC-34 cells and up-regulates its type II receptor.

Bone morphogenetic proteins (BMPs) regulate several aspects of neuronal behavior. For instance, BMP-2 has the ability to modulate, either positively or negatively, the outgrowth of neuronal processes in diverse cell types. In Drosophila motor neurons, the BMP type II receptor (BMPRII) homolog wishful thinking plays crucial roles on neuromuscular synaptogenesis signaling through Smad-dependent and Smad-independent pathways. However, a role for BMP signaling at the vertebrate neuromuscular junction has not been addressed. Herein, we have analyzed the expression of BMPRII and the effect of BMP-2 during the morphological differentiation of motor neuron-like NSC-34 cells. Our data indicate that BMPRII is up-regulated and becomes accumulated in somas and growth cones upon motor neuronal differentiation. BMP-2 inhibits the differentiation of NSC-34 cells, an effect that correlates with activation of a Smad-dependent pathway, induction of the inhibitory Id1 transcription factor, and down-regulation of the neurogenic factor Mash1. BMP-2 also activates effectors of Smad-independent pathways. Remarkably, BMP-2 treatment significantly increases the expression of BMPRII. Our findings provide the first evidence to suggest a role for BMP pathways on the differentiation of motor neurons leading to successful assembly and/or regeneration of the vertebrate neuromuscular synapse.

Sonic Hedgehog modulates EGFR dependent proliferation of neural stem cells during late mouse embryogenesis through EGFR transactivation.

Sonic Hedgehog (Shh/GLI) and EGFR signaling pathways modulate Neural Stem Cell (NSC) proliferation. How these signals cooperate is therefore critical for understanding normal brain development and function. Here we report a novel acute effect of Shh signaling on EGFR function. We show that during late neocortex development, Shh mediates the activation of the ERK1/2 signaling pathway in Radial Glial cells (RGC) through EGFR transactivation. This process is dependent on metalloprotease activity and accounts for almost 50% of the EGFR-dependent mitogenic response of late NSCs. Furthermore, in HeLa cancer cells, a well-known model for studying the EGFR receptor function, Shh also induces cell proliferation involving EGFR activation, as reflected by EGFR internalization and ERK1/2 phosphorylation. These findings may have important implications for understanding the mechanisms that regulate NSC proliferation during neurogenesis and may lead to novel approaches to the treatment of tumors.

DOT-ELISA en el diagnóstico presuntivo de la hidatidosis humana / DOT-ELISA in the presumptive diagnosis of the human hydatidosis

Se aplicó Dot-ELISA como método de diagnóstico presuntivo de la hidatidosis humana en 1616 muestras de sangre de personas aparentemente sanas procedentes de áreas rurales de la Provincia de Linares, VII Región, Chile. Las muestras se precesaron y ensayaron en el laboratorio del Hospital Base de Linares. La reacción de hemaglutinación indirecta (RHAI) y doble difusión con pesquisa del arco 5 de Caprón (DD5) se ejecutaron en el Laboratorio de Parasitología Campus Sur, como métodos diagnósticos de referencia. Con Dot-ELISA se observaron 112 sueros positivos (7,0 por ciento), con RHAI (2,4 por ciento) y con DD5 6 (0,4 por ciento). Se usó como criterio de probable infección por hidatidosis, cuando se constató positividad a las tres reacciones serológicas, que se observó en 5 casos (0,31 or ciento). Como criterio de sospecha de probable infección hidatídica con dos reacciones serológicas, situación que se presentó en 11 casos (0,68 por ciento). En estos momentos se estudian por exámenes de imagenología los individuos con posible infección hidatídica