Eosinophils oxidize damage-associated molecular pattern molecules derived from stressed cells.
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.
Lotfi
Ramin
R
Institut für klinische Transfusionsmedizin und Immungenetik Ulm, Institut für Transfusionsmedizin Universitat Ulm, Ulm, Germany.
Herzog
Gloria Isabelle
GI
DeMarco
Richard Anthony
RA
Beer-Stolz
Donna
D
Lee
James Joseph
JJ
Rubartelli
Anna
A
Schrezenmeier
Hubert
H
Lotze
Michael Thomas
MT
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology; D047093:Eosinophil Major Basic Protein / Q000276:immunology / Q000378:metabolism; D047209:Eosinophil Peroxidase / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009336:Necrosis / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010084:Oxidation-Reduction; D000067759:Receptor for Advanced Glycation End Products / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology*
D000906:Antibodies; D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011994:Recombinant Proteins; D047209:Eosinophil Peroxidase; D047093:Eosinophil Major Basic Protein