Eosinophils Do Not Enhance the Trans-Basement Membrane Migration of Neutrophils

Abstract

Background: There is increasing evidence that both neutrophilic and eosinophilic inflammation persist in the airways of patients with severe asthma. We have reported a positive relationship between the concentrations of eosinophils and neutrophils in sputum from severe asthmatics, suggesting a possible role of eosinophils in regulating neutrophilic inflammation. The aim of this study was to investigate whether activated eosinophils modify the trans-basement membrane migration (TBM) of neutrophils. Methods: Eosinophils and neutrophils were isolated from peripheral blood drawn from healthy donors. The TBM of neutrophils in response to a variety of chemoattractants was evaluated in the presence or absence of eosinophils by using the chambers with a Matrigel®-coated Transwell® insert. Results: As expected, eotaxin (10 nM) and RANTES (10 nM), but not IL-8 (10 nM), induced the TBM of eosinophils. On the contrary, only IL-8 induced the TBM of neutrophils. When eosinophils were coincubated with neutrophils and stimulated with IL-8, the TBM of eosinophils was significantly augmented. On the other hand, when neutrophils were coincubated with eosinophils and stimulated with eotaxin or RANTES, the TBM of neutrophils was not modified. Conclusions: Neutrophils migrated by IL-8 may lead eosinophils to accumulate in the airways of patients with severe asthma. On the other hand, it is unlikely that eosinophils migrated by chemoattractants such as CC chemokines regulate neutrophilic inflammation.

In vitro toxicity evaluation of diesel exhaust particles on human eosinophilic cell

“…This sequence of events is thought to enhance inflammation. A recent study has reported neutrophil migration by IL-8 possibly leads to eosinophilia in severe asthma (Kobayashi et al, 2007). In this study, IL-8 production by eosinophils increased by 10% due to DEPs exposure.…”

Phase 2, randomised placebo-controlled trial to evaluate the efficacy and safety of an anti-GM-CSF antibody (KB003) in patients with inadequately controlled asthma

“…It is possible that lower concentrations of GM-CSF are needed for an antiapoptotic effect on eosinophils than on neutrophils: 100 pg/mL vs 100 ng/mL, respectively. 18 38 Thus, in eosinophilic asthma where the eosinophil but not neutrophil numbers are high, the levels of GM-CSF in the lungs and airways may be very low (pg/mL) but still effective on eosinophils, and these low GM-CSF levels might have been neutralised at 400 mg dosing of KB003. Conversely, in neutrophilic asthma, where antiapoptosis of neutrophils may be important, the GM-CSF levels in lungs/airways required for such an effect may have to be higher (ng/mL).…”

Heterogeneity of asthma according to blood inflammatory patterns

“…As those with asthma with the EOS hi /NEU hi pattern were more often treated with ICS, the high eosinophil and neutrophil counts could be at least partially a consequence of steroid treatment, known to enhance neutrophil survival 28. Neutrophils may lead eosinophils to accumulate in the airways of patients with severe asthma and possibly aggravate the disease,29 and it is unlikely that eosinophils regulate neutrophilic inflammation 30. High eosinophil and neutrophil counts may also be related to exposure to specific environmental factors, in particular ozone, recently found to promote an antiapoptotic environment in allergen-primed animals 31.…”