Asthma therapy modulates priming-associated blood eosinophil responsiveness in allergic asthmatics

Abstract

Eosinophils play an important role in the pathogenesis of asthma. Several pro-inflammatory responses of eosinophils are primed in vivo in this disease. The aim of the present study was to investigate whether regular antiasthma treatment could modulate priming-sensitive cytotoxic mechanisms of human eosinophils.In a randomized, two-centre, double-blind parallel group study, the effect of 8 weeks of treatment with salmeterol xinafoate 50 mg b.i.d., beclomethasone dipropionate 400 mg b.i.d. or both on pulmonary function and the activation of primingsensitive cytotoxic mechanisms of eosinophils, i.e. degranulation of eosinophil cationic protein (ECP) in serum, and activation of isolated eosinophils in the context of induction of the respiratory burst and release of platelet-activating factor (PAF) were tested. These effects were evaluated in 40 allergic asthmatics before and 24 h after allergen inhalation challenge.Whereas baseline forced expiratory volume in one second (FEV1) improved in all treatment groups, only treatment with a combination of salmeterol and beclomethasone significantly inhibited the allergen-induced increase in serum ECP, and (primed/ unprimed) PAF-release, suggesting inhibition of eosinophil priming after allergen challenge. In contrast to the combination therapy, monotherapy with beclomethasone had no influence on allergen-induced PAF-release, suggesting an additional antiinflammatory effect of salmeterol during combination therapy. Monotherapy with beclomethasone inhibited the prechallenge serum-treated zymosan (STZ) (0.1 mg . mL -1 )-induced respiratory burst and the allergen-induced increase in serum ECP levels, reflecting pre-and postchallenge anti-inflammatory effects. During monotherapy with salmeterol, an allergen-induced increase in serum ECP concentration and STZ (0.1 mg . mL -1 )-induced respiratory burst was observed, suggesting that treatment with salmeterol alone had no effect on priming-sensitive eosinophil cytotoxic mechanisms.In conclusion, this study shows that standard asthma therapy leads to inhibition of eosinophil priming of cytotoxic mechanisms in vivo. Eur Respir J 1999; 14: 915±922.

Gradual increase in priming of human eosinophils during extravasation from peripheral blood to the airways in response to allergen challenge

“…Adhesion to surfaces, transendothelial migration, and chemotaxis were found to be enhanced in eosinophils isolated from the blood of patients with allergic asthma. 12,14,27,28 However, cytotoxic responses such as degranulation and activation of the respiratory burst were less sensitive for this in vivo priming process. 28 These findings are consistent with the hypothesis that early priming processes are focused on adhesion processes and prepare eosinophils to leave the peripheral blood to inflammatory loci.…”

“…12,14,27,28 However, cytotoxic responses such as degranulation and activation of the respiratory burst were less sensitive for this in vivo priming process. 28 These findings are consistent with the hypothesis that early priming processes are focused on adhesion processes and prepare eosinophils to leave the peripheral blood to inflammatory loci. Cytotoxic responses are then primed during transition from peripheral blood to the inflammatory loci.…”

“…[24][25][26] Several studies have demonstrated that priming is essential for several eosinophil responses isolated from the peripheral blood of patients with allergic asthma, and it is not the mere quantity of cells in the peripheral blood that is important. 11,12,27,28 Furthermore, many processes including adhesion, degranulation, and respiratory burst activated by physiological stimuli are optimally activated only provided that the cells have interacted with a priming agent. The most convincing data were acquired by measuring migratory-associated processes.…”

Respiratory symptoms among crab processing workers in Alaska: Epidemiological and environmental assessment*

“…In this investigation serum ECP was elevated among workers who developed asthma-like and bronchitic symptoms. Previous studies have shown a good correlation between subjects with asthma symptoms and increased levels of ECP [De Blay et al, 1998;Grutters et al, 1999].…”

Expression of activated FcγRII discriminates between multiple granulocyte-priming phenotypes in peripheral blood of allergic asthmatic subjects

“…27,30 Systemic inflammatory responses during the LAR have been described in several studies and were associated with an increase of blood eosinophil numbers that likely had a primed phenotype. [30][31][32] In this study the mechanisms involved in the systemic innate immune responses of allergic asthmatic subjects were investigated before and after allergen challenge. The allergen-induced priming of peripheral blood eosinophils and neutrophils was measured in atopic subjects with mild asthma with and without allergen-induced LAR.…”