Eosinophils oxidize damage-associated molecular pattern molecules derived from stressed cells

Ramin Lotfi, Gloria Isabelle Herzog, Richard Anthony DeMarco, Donna Beer-Stolz, James Joseph Lee, Anna Rubartelli, Hubert Schrezenmeier, Michael Thomas Lotze

Research output: Contribution to journalArticle

Abstract

Eosinophils (Eos) are found at increased numbers within necrotic areas of tumors. We show that necrotic material from cell lysates containing damage-associated molecular pattern molecules induce eosinophil degranulation (release of major basic protein and eosinophil peroxidase) and enhance their oxidative burst while the stimulatory capacity of cell lysates is significantly diminished following oxidation. High mobility group box 1 (HMGB1), a prototypic damage-associated molecular pattern molecule, released following necrosis but not apoptosis, induced a similar effect on Eos. Additionally, we demonstrate that HMGB1 enhances eosinophil survival and acts as a chemoattractant. Consistently, we show that Eos express an HMGB1 receptor, the receptor for advanced glycation end product, and that anti-receptor for advanced glycation end product could diminish the HMGB1-mediated effects. Of all tested biologic activities, Eos respond most sensitively to the presence of necrotic material including HMGB1 with generation of peroxide. We postulate that Eos "sense" necrotic cell death, migrating to and responding to areas of tissue injury/necrosis. Oxidation of cell lysates reduces their biologic activity when compared with native lysates. We postulate that eosinophil-associated modulation of immunity within tumor and other damaged tissues may be primarily by promoting oxidative degradation of necrotic material. Novel therapeutic strategies may be considered by advancing oxidative denaturation of released necrotic material using Eos or other aerobic strategies.

Original languageEnglish
Pages (from-to)5023-5031
Number of pages9
JournalJournal of Immunology
Volume183
Issue number8
DOIs
Publication statusPublished - Oct 15 2009

ASJC Scopus subject areas

  • Immunology

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    Lotfi, R., Herzog, G. I., DeMarco, R. A., Beer-Stolz, D., Lee, J. J., Rubartelli, A., Schrezenmeier, H., & Lotze, M. T. (2009). Eosinophils oxidize damage-associated molecular pattern molecules derived from stressed cells. Journal of Immunology, 183(8), 5023-5031. https://doi.org/10.4049/jimmunol.0900504