Neutrophils enhance eosinophil migration across monolayers of lung epithelial cells

Abstract

During the late-phase asthmatic response eosinophils and neutrophils infiltrate the lungs and cause severe damage. In this study, we investigated in vitro the migration of eosinophils, in the absence and presence of neutrophils, across a monolayer of lung H292 epithelial cells. The migration of eosinophils towards the complement fragment 5a (C5a) was increased when neutrophils were added to the upper compartment of the Transwells, and decreased when neutrophils were added to the lower compartment. Moreover, neutrophils exclusively stimulated eosinophil migration towards C5a, and not towards other chemoattractants such as RANTES, IL-8 or PAF. Neutrophils and eosinophils differed in that neutrophils, but not eosinophils, rapidly inactivated C5a, suggesting that neutrophils in the upper compartment remove part of the active C5a that has diffused into the upper compartment. Indeed, we found that the addition of other C5a-degrading agents, such as human serum or carboxypeptidase B, also enhanced eosinophil migration when added to the upper compartment and decreased migration when added to the lower compartment. Taken together, these results indicate that the presence of neutrophils influences the migratory behaviour of eosinophils in vitro. The neutrophils presumably maintain a proper C5a chemotactic gradient in the transmigration model, which results in enhanced eosinophil chemotaxis.

Diesel Exhaust Particulates Exacerbate Asthma-Like Inflammation by Increasing CXC Chemokines

“…The decreased pulmonary influx of eosinophils may be the direct result of reduced chemokine levels or an indirect result. In a study 66 using human lung epithelial cells, neutrophils stimulated eosinophils to move toward the complement fragment 5a. In another ex vivo system using isolated neutrophils and eosinophils, IL-8 (CXCL8) stimulated neutrophils to significantly enhance the trans-basement membrane migration of eosinophils.…”

Human Cathelicidin LL-37 Is a Chemoattractant for Eosinophils and Neutrophils That Acts via Formyl-Peptide Receptors

“…Furthermore, interactions between neutrophils and eosinophils were suggested in inflammatory lung diseases, as in a study demonstrating a more extensive eosinophil degranulation in children with acute severe asthma with a combined neutrophil/eosinophil airway inflammation, compared to patients with isolated eosinophilic inflammation [45]. In addition, eosinophil migration across layers of cultured epithelial cellswas enhanced by neutrophils, suggesting involvement of neutrophil-eosinophil interactions [46]. A mechanistic basis for interactions between neutrophils and eosinophils was provided by studies suggesting that neutrophil elastase [47,48,49] and eosinophilic major basic protein [50, 51] may mediate these interactions.…”

Association between Neutrophilic and Eosinophilic Inflammation in Patients with Severe Persistent Asthma

“…LTB 4 and TNF-␣ are also able to induce both accumulation and activation of eosinophils, and therefore these mediators should be taken into account in studying the mechanism for the simultaneous accumulation of both neutrophils and eosinophils observed with severe asthma. Another mechanism which may be involved in the association between neutrophils and eosinophils may be the activation of neutrophils: neutrophils by themselves, when activated, can secret mediators such as platelet activation factor, LTB 4 , and TNF-␣ [10][11][12][13] and may hence augment the accumulation of eosinophils. Therefore, it is theoretically possible that the presence of neutrophilic infl ammation, which persists even under full corticosteroid therapy, may contribute to the manifestation of severe asthma, at least in part, via the control of eosinophilic infl ammation.…”

“…In this context, Zuurbier et al [11] reported that neutrophils accelerate the transendothelial migration of eosinophils in vitro.…”