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Augmented TNF‐α and IL‐10 production by primed human monocytes following interaction with oxidatively modified autologous erythrocytes
Author(s) -
Liese Amy M.,
Siddiqi Muhammad Q.,
Siegel John H.,
Denny Thomas,
Spolarics Zoltán
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.2.289
Subject(s) - zymosan , lipopolysaccharide , cytokine , tumor necrosis factor alpha , monocyte , cd14 , biology , whole blood , immunology , flow cytometry , endocrinology , biochemistry , in vitro
The presence of dysfunctional/damaged red blood cells (RBCs) has been associated with adverse clinical effects during the inflammatory response. The aim of this study was to elucidate whether oxidatively modified, autologous RBCs modulate monocyte cytokine responses in humans. Monocyte tumor necrosis factor α (TNF‐α) and IL‐10 production was measured in whole blood from healthy volunteers using ELISA and flow cytometry. Oxidatively modified RBCs (15 mM phenylhydrazine, 1 h, OX‐RBC) or vehicle‐treated RBCs (VT‐RBC) opsonized by autologous serum were administered alone or in combination with one of three priming agents: E. coli lipopolysaccharide (LPS, 0.2 ng/ml), zymosan A (1 mg/ml), or phorbol 12‐myristate 13‐acetate (PMA, 50 ng/ml). OX‐RBC or VT‐RBC alone did not result in the release of TNF‐α or IL‐10. LPS, zymosan, and PMA caused marked and dose‐dependent increases in TNF‐α and IL‐10 production. Addition of OX‐RBC augmented the LPS‐, zymosan‐, and PMA‐induced TNF‐α release by approximately 100%. OX‐RBC augmented LPS‐ and zymosan‐induced IL‐10 release by 400–600%. Flow cytometry analyses showed that monocytes were responsible for TNF‐α and IL‐10 production in whole blood. The presence of OX‐RBC alone increased the complexity of CD14+ monocytes but caused no cytokine production. LPS alone induced cytokine production without altering cell complexity. After the combined (OX‐RBC+LPS) treatment, monocytes of high complexity were responsible for TNF‐α production. The presence of mannose or galactose (at 10–50 mM) did not alter the observed augmentation of cytokine production by OX‐RBC, suggesting that lectin receptors are not involved in the response. These studies indicate that the interaction between damaged autologous erythrocytes and monocytes has a major impact on the cytokine responses in humans. An augmented cytokine production by the mononuclear phagocyte system may adversely affect the clinical course of injury and infections especially in genetic or acquired RBC diseases or after transfusions.