Modulation of Eosinophil Chemotaxis by Interleukin-5

Abstract

Eosinophilia and eosinophil function are regulated by cytokines such as granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5). We have investigated the modulatory role of IL-5 on N-formyl-methionyl-leucyl-phenylalanine (FMLP), neutrophil-activating factor (NAF/IL-8), platelet factor 4 (PF4), and cytokine-induced chemotaxis of eosinophils from normal individuals. These eosinophils show a small chemotactic response toward PF4 but not to NAF/IL-8 and FMLP. Preincubation of eosinophils with low concentrations of IL-5 caused significantly increased responses toward PF4 and induced a significant chemotactic response toward FMLP and NAF/IL-8. In marked contrast, IL-5 (or IL-3) priming of eosinophils from normal donors resulted in a strong inhibition of GM-CSF-induced chemotaxis. A similar decrease in the chemotactic response toward GM-CSF was observed in eosinophils derived from allergic asthmatic individuals. This finding suggests that the latter eosinophils may have had a prior exposure to IL-5 (or IL-3). Washing of the cells after priming did not abrogate the inhibition of the GM-CSF response. Our data indicate that at low concentrations IL-5 is an important modulator of eosinophil chemotaxis, causing selective upregulation or downregulation of chemotactic responses toward different agents.

Upregulated response to chemokines in oxidative metabolism of eosinophils in asthma and allergic rhinitis

“…Moreover, the augmentative effect of IL-5 was observed only in eosinophils from normal subjects and not in those from allergic patients. This distinct phenotype is in line with data demonstrating in vivo priming of adhesion-associated responses of peripheral blood eosinophils of patients with allergic diseases [13,14]. Therefore, eosinophils from allergic patients may undergo IL-5 exposure in the blood stream, resulting in great enhancement of responsiveness to chemokines, as demonstrated in the present study.…”

“…Effect of interleukin-5 on chemokine-primed reactive oxygen species production by eosinophils IL-5 has been shown to enhance the effector function of eosinophils [12,13]. IL-5 augments eosinophil responses to -Reactive oxygen species (ROS) production by eosinophils treated with eotaxin (1-100 nM) from normal (h; n=12) and allergic (u; n =15) subjects as determined by maximal (a, c) and integral (b, d) intensity luminol-dependent chemiluminescence for 60 min.…”

“…platelet-activating factor, formyl-methionyl-leucyl-phenylalanine, platelet factor-4 and complement factor 5a [13,14]. Therefore, the possible involvement of IL-5 in the different eosinophil responses to chemokines between normal subjects and patients was examined.…”

Hydroxycarbamide reduces eosinophil adhesion and degranulation in sickle cell anaemia patients

“…Ex vivo eosinophil migratory and adhesive properties, as well as their capacity to degranulate, are significantly augmented in SCA, suggesting that these cells circulate in an activated state, as has been previously demonstrated in their neutrophil counterpart in SCA (Canalli et al, 2007). This activation has also been observed in other diseases, such as in allergies, where eosinophils present higher chemotactic activities (Sehmi et al, 1992;Warringa et al, 1992;Bruijnzeel et al, 1993;Ferreira et al, 2002).…”

Biology of interleukin‐5 and its relevance to allergic disease

“…Eosinophils and basophils are two predominant effector cell types involved in allergic inflammation. In vifro, IL-5 affects eosinophi1 growth and differentiation (7,8,58,59), migration (10,58,60), activation and effector function (58,61,62), and survival (58,63). TL-3 and GM-CSF are also maturation and growth factors for human eosinophils (64), but eosinophils treated with IL-3 and CM-CSF remain immature.…”