Activation states of blood eosinophils in asthma

Abstract

Asthma is characterized by airway inflammation rich in eosinophils. Airway eosinophilia is associated with exacerbations and has been suggested to play a role in airway remodeling. Recruitment of eosinophils from the circulation requires that blood eosinophils become activated, leading to their arrest on the endothelium and extravasation. Circulating eosinophils can be envisioned as potentially being in different activation states, including non-activated, pre-activated or “primed”, or fully activated. In addition, the circulation can potentially be deficient of pre-activated or activated eosinophils, because such cells have marginated on activated endothelium or extravasated into the tissue. A number of eosinophil-surface proteins, including CD69, L-selectin, intercellular adhesion molecule-1 (ICAM-1, CD54), CD44, P-selectin glycoprotein ligand-1 (PSGL-1, CD162), cytokine receptors, Fc receptors, integrins including αM integrin (CD11b), and activated conformations of Fc receptors and integrins have been proposed to report cell activation. Variation in eosinophil activation states may be associated with asthma activity. Eosinophil-surface proteins proposed to be activation markers, with a particular focus on integrins, and evidence for associations between activation states of blood eosinophils and features of asthma are reviewed here. Partial activation of β1 and β2 integrins on blood eosinophils, reported by monoclonal antibodies (mAb) N29 and KIM-127, is associated with impaired pulmonary function and airway eosinophilia, respectively, in non-severe asthma. The association with lung function does not occur in severe asthma, presumably due to greater eosinophil extravasation, specifically of activated or pre-activated cells, in severe disease.

Increased CD69 Expression on Peripheral Eosinophils from Patients with Food Protein-Induced Enterocolitis Syndrome

“…Although we do not know whether such activation is an initial event triggered by food antigens or reflects a secondary immune response following intense systemic reactions, it seems reasonable to assume that eosinophils in the intestinal mucosal tissue are also activated, resulting in degranulation of various inflammatory mediators, including EDN. Similar results were obtained from a 8 study of eosinophils from patients with bronchial asthma, where CD69 was expressed both on locally activated lung eosinophils and on circulating eosinophils after an in vivo challenge with inhalation allergens [18,19]. In addition, severe cases of atopic dermatitis exhibited systemic allergic inflammation, resulting in expansion of activated eosinophils in the peripheral blood [10].…”

A pathophysiological role of PDE3 in allergic airway inflammation

“…Given the fast antiallergic response, we investigated whether PDE3 effects on integrin might be associated in allergic airway inflammation. Mouse and human eosinophils express CD11b, an integrin that is crucial for immune cell extravasation (60). Elevated levels of CD11b in neutrophils and eosinophils were seen in affected lung tissue when compared with blood levels (61).…”

CD81 and CD48 show different expression on blood eosinophils in systemic sclerosis: new markers for disease and pulmonary inflammation?

“…Fluorescein isothiocyanate (FITC)-labelled anti-CD16 and peridine-chlorophyll protein Cy5.5 (PerCP-Cy5.5)-labelled anti-CD9 antibodies, both of IgG1 isotype (clone 3G8 and M-L13 respectively; BD Bioscience, San Jose, CA) were used for identification of eosinophil granulocytes. We selected a panel of activation marker that had previously been applied in studies of eosinophils, as reviewed in [14]. Surface molecules were assessed using phycoerythrin-labelled antibodies.…”