Cytokine generation by eosinophils,☆☆,,★★

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IL-1α

The early observation of Del Pozo et al.13 that murine eosinophils expressed mRNA for IL-1α, as detected by the technique of in situ hybridization, led to subsequent studies on the ability of eosinophils to synthesize and release cytokines. Messenger RNA in murine peritoneal eosinophils, stimulated for 6 hours with lipopolysaccharide, were hybridized with a 35S-labeled cDNA probe for IL-1α. IL-1α was also detected in supernatants from these stimulated cells.

The ability of human eosinophils to

Transforming growth factor–α

Wong et al.,15 while investigating oral squamous carcinoma, known to be associated with increases in the level of tissue eosinophils, detected transforming growth factor–α (TGF-α) at the tumor site. They were able to colocalize mRNA and the protein to the eosinophils. The observation was confirmed by examining peripheral blood eosinophils from patients with hypereosinophilic syndrome. Eosinophils, both in vivo and in vitro, appeared to have a constitutive expression of mRNA for TGF-α. This

GM-CSF

Moqbel et al.21 used in situ hybridization to demonstrate that normal density human eosinophils (obtained by metrizamide gradient separation) transcribed and translated mRNA for GM-CSF after stimulation with either IFN-γ or the calcium ionophore A23187. GM-CSF mRNA was colocalized to the stimulated eosinophil with a combination of in situ hybridization and histochemistry (carbol chromotrope 2R) or immunochemistry (EG2).21 Kita et al.22 also demonstrated eosinophil-derived GM-CSF after

IL-3

Kita et al.,22 while studying the release of GM-CSF from eosinophils stimulated with ionomycin, were also able to detect IL-3 in the same supernatants. IL-3 is also known to prolong survival of eosinophils and therefore may be an additional autocrine factor that can be produced and utilized by the eosinophil after stimulation. To date, IL-3 mRNA expression in eosinophils, either in vitro or in vivo, has not been demonstrated.

IL-5

Desreumaux et al.30 made the interesting observation that eosinophils infiltrating mucosa of patients with active coeliac disease express mRNA for IL-5. IL-5 mRNA+ cells were found in diseased but not normal tissue and were absent after treatment with a gluten-free diet. By in situ hybridization, mRNA was identified in peripheral blood of eosinophilic subjects. IL-5 mRNA expression in eosinophils in vivo was also demonstrated in bronchoalveolar lavage cells obtained from asthmatic subjects.26

IL-6

Using a similar approach to that of GM-CSF, IL-6 mRNA was also found in normal density eosinophils.33 Approximately 20% of unstimulated eosinophils were IL-6 mRNA+, whereas the level of expression was enhanced after stimulation with IFN-γ. Translation of mRNA was detected by immunocytochemistry, which showed that staining for IL-6 was “granular.” We were also able to measure the release of IL-6 in the supernatant of cultured eosinophils before and after stimulation.33 This observation has been

IL-8

Highly purified eosinophils cultured in vitro with calcium ionophore released IL-8 into the supernatant as shown by specific ELISA.35 This was inhibited both by cyclosporine and cyclohexamide, an inhibitor of protein synthesis. IL-8 mRNA was demonstrated by PCR amplification after stimulation. The presence of immunoreactive IL-8 was also detected using immunocytochemical staining with use of a monoclonal antibody against IL-8. Here again the staining was granular, which suggests that the

TNF-α

Again, using the technique of in situ hybridization, 44% to 100% of eosinophils obtained from the peripheral blood or healthy subjects or patients with hypereosinophilia were positive for TNF-α mRNA.37 The presence of the protein in blood eosinophils from hypereosinophilic subjects was also detected by immunocytochemical staining. When eosinophils were purified from atopic persons, spontaneous release of TNF-α in vitro was inhibitable by cyclohexamide pretreatment. Infiltrating eosinophils in

MACROPHAGE INFLAMMATORY PROTEIN–1α

In the same study by Costa et al.,37 a high percentage of blood eosinophils (39% to 91%) obtained from hypereosinophilic patients showed positive mRNA expression for the chemokine macrophage inflammatory protein–1α (MIP-1α). Eosinophils obtained from normal donors had weak or undetectable expression of this chemokine. In vivo, most eosinophils that infiltrated nasal polyp tissue had strong expression for MIP-1α mRNA. This observation was confirmed by Northern blot analysis.

CONCLUSIONS

Eosinophils synthesize, store, and release a wide array of cytokines, as well as basic granule-derived proteins and lipid mediators. This functional versatility has several implications for the potential role of the eosinophil in allergic tissue reactions. Eosinophils might act to amplify the allergic response, which, in asthma for example, would enhance tissue damage, but in helminth infections could promote adaptive immunity. On the other hand, eosinophil cytokine production may be a

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  • Cited by (0)

    From the Department of Allergy and Clinical Immunology, National Heart and Lung Institute.

    ☆☆

    Reprints are not available.

    Correspondence: R. Moqbel, PhD, Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom.

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