Echinococcus granulosus Antigen B binds to monocytes and macrophages modulating cell response to inflammation

Background: Antigen B (EgAgB) is an abundant lipoprotein released by the larva of the cestode Echinococcus granulosus into the host tissues. Its protein moiety belongs to the cestode-specific family known as hydrophobic ligand binding protein (HLBP), and is encoded by five gene subfamilies (EgAgB8/1-EgAgB8/5). The functions of EgAgB in parasite biology remain unclear. It may play a role in the parasite's lipid metabolism since it carries host lipids that E. granulosus is unable to synthesise. On the other hand, there is evidence supporting immuno-modulating activities in EgAgB, particularly on innate immune cells. Both hypothetical functions might involve EgAgB interactions with monocytes and macrophages, which have not been formally analysed yet. Methods: EgAgB binding to monocytes and macrophages was studied by flow cytometry using inflammation-recruited peritoneal cells and the THP-1 cell line. Involvement of the protein and phospholipid moieties in EgAgB binding to cells was analysed employing lipid-free recombinant EgAgB subunits and phospholipase D treated-EgAgB (lacking the polar head of phospholipids). Competition binding assays with plasma lipoproteins and ligands for lipoprotein receptors were performed to gain information about the putative EgAgB receptor(s) in these cells. Arginase-I induction and PMA/LPS-triggered IL-1 beta, TNF-alpha and IL-10 secretion were examined to investigate the outcome of EgAgB binding on macrophage response. Results: Monocytes and macrophages bound native EgAgB specifically; this binding was also found with lipid-free rEgAgB8/1 and rEgAgB8/3, but not rEgAgB8/2 subunits. EgAgB phospholipase D-treatment, but not the competition with phospholipid vesicles, caused a strong inhibition of EgAgB binding activity, suggesting an indirect contribution of phospholipids to EgAgB-cell interaction. Furthermore, competition binding assays indicated that this interaction may involve receptors with affinity for plasma lipoproteins. At functional level, the exposure of macrophages to EgAgB induced a very modest arginase-I response and inhibited PMA/LPS-mediated IL-1 beta and TNF-alpha secretion in an IL-10-independent manner. Conclusion: EgAgB and, particularly its predominant EgAgB8/1 apolipoprotein, are potential ligands for monocyte and macrophage receptors. These receptors may also be involved in plasma lipoprotein recognition and induce an anti-inflammatory phenotype in macrophages upon recognition of EgAgB

Manejo de las hiperplasias linfoides orbitarias / Management of lymphoid hyperplasia of the ocular adnexa

Objetivo: La hiperplasia linfoide (HL) es una proliferación benigna e hipercelular, rica en linfocitos, que morfológicamente puede simular un linfoma. Su incidencia ha disminuido debido a la sofisticación de las técnicas diagnósticas y mejor conocimiento de los linfomas. Se presenta entre la 4.ª y 6.ª década de la vida y no está determinado un manejo apropiado, objetivo de nuestro trabajo.Método: Se ha estudiado tres pacientes con alteración linfoproliferativa de anexos oculares en los que se aplicó las técnicas de histología, inmunohistoquímica y biología molecular y cuyo diagnostico definitivo se realizó gracias a la reacción en cadena de la polimerasa (PCR).Resultados: Las tres muestras fueron diagnosticadas por histología de HL, con las técnicas inmunohistoquímicas el resultado fue de una inflamación orbitaria idiopática y las otras dos restantes de HL. La PCR diagnosticó un linfoma no-Hodgkiniano tipo B y la otra muestra confirmó una HL.Conclusión: Hoy en día las técnicas de biología molecular son las que permiten definir que es un linfoma, en algunos casos sólo la histología y la inmunohistoquímica pueden inducir a error. Las HL de los anexos pueden suponer un estado inicial de la enfermedad. El hallazgo de una hiperplasia presumiblemente benigna en dicha localización debe hacer sospechar un posible linfoma. El diagnóstico de linfoma está en continuo cambio debido a la sofisticación de las técnicas diagnósticas. Por tanto el diagnóstico de una HL inicialmente benigna, obliga a realizar una exploración sistémica y a un seguimiento de los pacientes estrecho y muy minucioso

Objective: Lymphoid Hyperplasia (LH) is a benign proliferative lymphocyte-rich process. Histologically, LH may be similar to a lymphoma. Its incidence has decreased because of new sophisticated diagnostic procedures and a better knowledge of lymphomas. Most of the cases are seen in patients between forty and sixty years of age. As there was no consensus about the best treatment, determining this was the objective of our study. Method: We describe three patients with a lymphoproliferative process affecting the ocular anexae, in whom histologic, immuno-histochemical and molecular studies were performed. PCR analysis allowed a definitive diagnosis to be made. Results: Histologically, all three cases were diagnosed as LH; immuno-histochemically, one was diagnosed as an idiopathic orbital inflammation, and the other two, as LH. After PCR analysis, one of these latter two cases was definitively diagnosed as B-cell Non-Hodgkin’s lymphoma. Conclusions: Today’s molecular techniques allow us to make a definite diagnosis of lymphoma, because sometimes histology and immuno-histochemistry alone can result in a wrong diagnosis being made. LH of the ocular adnexae may be the first stage of a much more serious disease, and a benign hyperplasia at this site must lead to suspicion of lymphoma, which can then be diagnosed or excluded by the improved diagnostic procedures. Therefore, when we make a diagnosis of LH it is necessary to complete a full evaluation and institute a defined follow-up of the patient’s clinical condition