Coordinated regulation of eosinophil production and migration by glucocorticoids, prostaglandins, and cysteinyl-leukotrienes.

Introduction: The spectrum of eosinophil functions has expanded from fighting helminths to multiple novel roles in malignancy, infection, cancer, and metabolism. In asthma, glucocorticoids, prostaglandins (PG), and cysteinyl-leukotrienes (LT) regulate eosinophil biology through separate signaling pathways. Here we've evaluated the complex interplay between Dexa, PGE2, and CysLTs in eosinopoiesis and eosinophil biology in an allergic asthma model.

5-lipoxygenase- and Glucocorticoid-dependent eosinophilia in a novel surgical model in mice.

Background: Subcutaneous implants of heat-coagulated egg white (egg white implants, EWI) induce intense local eosinophilia and prime for hyperreactivity following airway ovalbumin challenge. The roles of allergen sensitization, surgical trauma-induced glucocorticoids, and the 5-lipoxygenase (5-LO) pathway were hitherto unexplored in this model, in which quantitative recovery and large-scale purification of the eosinophils from the inflammatory site for functional and immunopharmacological studies are difficult to achieve.

Methods: We overcame this limitation by shifting the implantation site to the peritoneal cavity (EWIp), thereby enabling quantitative leukocyte retrieval.

Allergen challenge-induced changes in bone-marrow responses to leukotriene D, nonsteroidal anti-inflammatory drugs and cytokines.

In nonallergic (naive) mice, type I cysteinyl-leukotriene receptors (CysLTR) mediate the stimulatory effects of cytokines (eotaxin/CCL11, interleukin[IL] - 13), and nonsteroidal anti-inflammatory drugs (NSAID; indomethacin, aspirin) on eosinophil production by IL-5-stimulated bone-marrow. In ovalbumin (OVA)-sensitized mice, airway challenge-induced bone-marrow eosinophilia and eosinopoiesis are prevented by pretreatment with blockers of adrenal glucocorticoid signaling (RU486, metyrapone) or cysteinyl-leukotriene (CysLT) signaling (montelukast). To define whether allergen challenge modifies subsequent bone-marrow responses to CysLT, NSAID, and cytokines which act through type 1 CysLT receptor (CysLTR).

Potent stimulation of eosinopoiesis in murine bone-marrow by myriadenolide is mediated by cysteinyl-leukotriene signaling.

We describe the potent effect of myriadenolide (Myr), a naturally occurring labdane diterpene, in promoting the production of eosinophils in cultured bone-marrow from several inbred mouse strains. This enhancing effect is lineage-selective and requires the eosinophil growth factors, Interleukin(IL)-5 or GM-CSF. Myr acts over a very low concentration range (10-10 M), if added at the beginning of the cell cultivation.

The Need to Consider Context in the Evaluation of Anti-infectious and Immunomodulatory Effects of Vitamin A and its Derivatives.

Vitamin A and its derivatives (retinoids) act as potent regulators in many aspects of mammalian reproduction, development, repair, and maintenance of differentiated tissue functioning. Unlike other vitamins, Vitamin A and retinoids, which have hormonal actions, present significant toxicity, which plays roles in clinically relevant situations, such as hypervitaminosis A and retinoic acid ("differentiation") syndrome. Although clinical presentation is conspicuous in states of insufficient or excessive Vitamin A and retinoid concentration, equally relevant effects on host resistance to specific infectious agents, and in the general maintenance of immune homeostasis, may go unnoticed, because their expression requires either pathogen exposure or the presence of inflammatory co-morbidities.