Blood eosinophil numbers may be elevated in allergy, inflammatory bowel disease and eosinophilic esophagitis. The aim of this study was to examine whether circulating eosinophils display distinct phenotypes in these disorders and if different patterns of eosinophilic chemoattractants exist. Blood eosinophils from patients with symptomatic eosinophilic esophagitis (EoE; n = 12), ulcerative colitis (n = 8), airway allergy (n = 10) and healthy controls (n = 10) were enumerated and their surface markers analyzed by flow cytometry. Plasma levels of pro-eosinophilic cytokines were quantified in parallel. Data were processed by multivariate pattern recognition methods to reveal disease-specific patterns of eosinophil phenotypes and cytokines. EoE patients had higher numbers of eosinophils with enhanced expression of CD23, CD54, CRTH2 and CD11c and diminished CCR3 and CD44 expression. Plasma CCL5 was also increased in EoE. Although allergic patients had increased interleukin (IL)-2, IL-3, IL-5 and granulocyte macrophage colony-stimulating factor plasma concentrations, their blood eosinophil phenotypes were indistinguishable from those of healthy controls. Decreased eosinophilic expression of CD11b, CD18, CD44 and CCR3, but no distinctive pattern of eosinophil chemoattractants, characterized ulcerative colitis. We propose that eosinophils acquire varying functional properties as a consequence of distinct patterns of activation signals released from the inflamed tissues in different diseases.

Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.

While increased numbers of eosinophils may be detected in patients with graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation, it is not known if eosinophils play a role in GVHD. The aims of this study were to determine: whether eosinophils are activated during GVHD; whether the patterns of activation are similar in acute and chronic GVHD; and the ways in which systemic corticosteroids affect eosinophils. Transplanted patients (n = 35) were investigated for eosinophil numbers and the expression levels of 16 eosinophilic cell surface markers using flow cytometry; all the eosinophil data were analyzed by the multivariate method OPLS-DA. Different patterns of molecule expression were observed on the eosinophils from patients with acute, chronic, and no GVHD, respectively. The molecules that provided the best discrimination between acute and chronic GVHD were: the activation marker CD9; adhesion molecules CD11c and CD18; chemokine receptor CCR3; and prostaglandin receptor CRTH2. Patients with acute or chronic GVHD who received systemic corticosteroid treatment showed down-regulation of the cell surface markers on their eosinophils, whereas corticosteroid treatment had no effect on the eosinophil phenotype in the patients without GVHD. In summary, eosinophils are activated in GVHD, display different activation profiles in acute and chronic GVHD, and are highly responsive to systemic corticosteroids.

Eosinophils express the chemoattractant receptors CCR3 and FPR. CCR3 binds several agonists such as eotaxin-1, -2, and -3 and RANTES, whereas the FPR binds the formylated tripeptide fMLP and a host of other ligands. The aim of this study was to investigate if there is interplay between these two receptors regarding the elicitation of migration and respiratory burst in human blood-derived eosinophils. Inhibition of the FPR with the antagonists CyH and boc-MLP abrogated the migration of eosinophils toward all of the CCR3 agonists. Similar results were seen when the FPR was desensitized with its cognate ligand, fMLP. In contrast, the respiratory burst triggered by eotaxin-1 was not inhibited by CyH. Thus, signals evoked via the FPR caused unidirectional down-regulation of CCR3-mediated chemotaxis but not respiratory burst in human eosinophils. The underlying mechanism was neither reduced ability of the CCR3 ligand eotaxin-1 to bind to CCR3 nor down-regulation of CCR3 from the cell surface. Finally, confocal microscopy and adFRET analysis ruled out homo- or heterodimer formation between FPR and/or CCR3 as an explanation for the reduction in chemotaxis via CCR3. Pharmacologic inhibition of signal transduction molecules showed that the release of free oxygen radicals in response to eotaxin-1 compared with fMLP is relatively more dependent on the p38 MAPK pathway.

The effects of preload and afterload on the performance of the systemic heart of the hagfish Myxine glutinosa were investigated before and during sotalol treatment using an in situ perfusion technique. Elevation of input pressure (preload) increased flow by means of increased stroke volume and heart rate in accordance with Starling's law of the heart, while increased output pressure (afterload) decreased flow mainly because of decreased stroke volume. Treatment with the beta-adrenoceptor antagonist sotalol did not change the quality of the responses to increased preload or afterload, although power output decreased by 40 % and flow rate was reduced by 35 % mainly due to a decrease in heart rate. Isolated preparations of the systemic heart and the portal heart provided information on the chronotropic effects of different agonists and antagonists. Both the systemic heart and the portal heart were insensitive to adrenergic and cholinergic agonists, adrenocorticotropic hormone and the cholinoceptor antagonist atropine. Sotalol treatment lowered the rate of spontaneous contractions by 30 % in the systemic heart preparation and by 21 % in the portal heart preparation. This study has given further evidence for the existence of a tonic beta-adrenoceptor stimulation of the hagfish systemic heart and portal heart, and demonstrated the importance of that stimulation in maintaining systemic heart performance.