Response of Neutrophils to Extracellular Haemoglobin and LTA in Human Blood System
Background: Haemolytic infection lyses red blood cells, releasing haemoglobin (Hb) into the plasma. Although recent studies showed that immune cells recognize redox-active cytotoxic extracellular Hb (metHb) bound to pathogen-associated molecular patterns (PAMPs), currently available information is l...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-03-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396415000043 |
| _version_ | 1819205072563732480 |
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| author | Sae-Kyung Lee Suh Yee Goh Yuan Qi Wong Jeak Ling Ding |
| author_facet | Sae-Kyung Lee Suh Yee Goh Yuan Qi Wong Jeak Ling Ding |
| author_sort | Sae-Kyung Lee |
| collection | DOAJ |
| description | Background: Haemolytic infection lyses red blood cells, releasing haemoglobin (Hb) into the plasma. Although recent studies showed that immune cells recognize redox-active cytotoxic extracellular Hb (metHb) bound to pathogen-associated molecular patterns (PAMPs), currently available information is limited to experiments performed in defined conditions using single cell lines. Therefore, a systemic approach targeting primary whole blood cells is required to better understand the cellular immune defence against metHb and PAMPs, when under a haemolytic infection.
Methods: We investigated how human white blood cells, including neutrophils, respond to metHb and lipoteichoic acid (LTA) by measuring reactive oxygen species (ROS), signalling mediators (ERK and p38), NF-κB, cytokines, elastase secretion and cell activation markers.
Findings: metHb activates NF-κB in TLR2-expressing HEK293 cells but not in normal or TLR9-expressing HEK293 cells. Treatment of isolated neutrophils with metHb increased production of ROS and expressions of IL-8, TNFα, and CD11b, which were further enhanced by metHb + LTA complex. While LTA stimulated the survival of neutrophils, it caused apoptotic cell death when complexed with metHb. The activation of neutrophils by metHb + LTA was subdued by the presence of other types of white blood cells.
Interpretation: metHb and metHb + LTA complex are ligands of TLR2, inducing an unconventional TLR signalling pathway. Neutrophils are a highly sensitive cell type to metHb + LTA complex. During a haemolytic infection, white blood cells in the vicinity crosstalk to modulate neutrophil TLR-signalling induced by metHb and LTA. |
| first_indexed | 2024-12-23T04:45:53Z |
| format | Article |
| id | doaj.art-62f9fdb5f5af4345af2ac7b4d3b8da8e |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-23T04:45:53Z |
| publishDate | 2015-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-62f9fdb5f5af4345af2ac7b4d3b8da8e2022-12-21T17:59:38ZengElsevierEBioMedicine2352-39642015-03-012322523310.1016/j.ebiom.2015.01.003Response of Neutrophils to Extracellular Haemoglobin and LTA in Human Blood SystemSae-Kyung LeeSuh Yee GohYuan Qi WongJeak Ling DingBackground: Haemolytic infection lyses red blood cells, releasing haemoglobin (Hb) into the plasma. Although recent studies showed that immune cells recognize redox-active cytotoxic extracellular Hb (metHb) bound to pathogen-associated molecular patterns (PAMPs), currently available information is limited to experiments performed in defined conditions using single cell lines. Therefore, a systemic approach targeting primary whole blood cells is required to better understand the cellular immune defence against metHb and PAMPs, when under a haemolytic infection. Methods: We investigated how human white blood cells, including neutrophils, respond to metHb and lipoteichoic acid (LTA) by measuring reactive oxygen species (ROS), signalling mediators (ERK and p38), NF-κB, cytokines, elastase secretion and cell activation markers. Findings: metHb activates NF-κB in TLR2-expressing HEK293 cells but not in normal or TLR9-expressing HEK293 cells. Treatment of isolated neutrophils with metHb increased production of ROS and expressions of IL-8, TNFα, and CD11b, which were further enhanced by metHb + LTA complex. While LTA stimulated the survival of neutrophils, it caused apoptotic cell death when complexed with metHb. The activation of neutrophils by metHb + LTA was subdued by the presence of other types of white blood cells. Interpretation: metHb and metHb + LTA complex are ligands of TLR2, inducing an unconventional TLR signalling pathway. Neutrophils are a highly sensitive cell type to metHb + LTA complex. During a haemolytic infection, white blood cells in the vicinity crosstalk to modulate neutrophil TLR-signalling induced by metHb and LTA.http://www.sciencedirect.com/science/article/pii/S2352396415000043Haemolytic infectionLeukocytesExtracellular haemoglobinLipoteichoic acidReactive oxygen speciesStaphylococcus aureusToll like receptor |
| spellingShingle | Sae-Kyung Lee Suh Yee Goh Yuan Qi Wong Jeak Ling Ding Response of Neutrophils to Extracellular Haemoglobin and LTA in Human Blood System EBioMedicine Haemolytic infection Leukocytes Extracellular haemoglobin Lipoteichoic acid Reactive oxygen species Staphylococcus aureus Toll like receptor |
| title | Response of Neutrophils to Extracellular Haemoglobin and LTA in Human Blood System |
| title_full | Response of Neutrophils to Extracellular Haemoglobin and LTA in Human Blood System |
| title_fullStr | Response of Neutrophils to Extracellular Haemoglobin and LTA in Human Blood System |
| title_full_unstemmed | Response of Neutrophils to Extracellular Haemoglobin and LTA in Human Blood System |
| title_short | Response of Neutrophils to Extracellular Haemoglobin and LTA in Human Blood System |
| title_sort | response of neutrophils to extracellular haemoglobin and lta in human blood system |
| topic | Haemolytic infection Leukocytes Extracellular haemoglobin Lipoteichoic acid Reactive oxygen species Staphylococcus aureus Toll like receptor |
| url | http://www.sciencedirect.com/science/article/pii/S2352396415000043 |
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