Low-Density Neutrophils Contribute to Subclinical Inflammation in Patients with Type 2 Diabetes

Type 2 diabetes (T2D) is characterized by low-grade inflammation. Low-density neutrophils (LDNs) represent normally less than 2% of total neutrophils but increase in multiple pathologies, releasing inflammatory cytokines and neutrophil extracellular traps (NETs). We assessed the count and role of hi...

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Published inInternational journal of molecular sciences Vol. 25; no. 3; p. 1674
Main Authors Dumont, Benjamin L., Neagoe, Paul-Eduard, Charles, Elcha, Villeneuve, Louis, Tardif, Jean-Claude, Räkel, Agnès, White, Michel, Sirois, Martin G.
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Published Switzerland MDPI AG 01.02.2024
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Abstract Type 2 diabetes (T2D) is characterized by low-grade inflammation. Low-density neutrophils (LDNs) represent normally less than 2% of total neutrophils but increase in multiple pathologies, releasing inflammatory cytokines and neutrophil extracellular traps (NETs). We assessed the count and role of high-density neutrophils (HDNs), LDNs, and NET-related activities in patients with T2D. HDNs and LDNs were purified by fluorescence-activated cell sorting (FACS) and counted by flow cytometry. Circulating inflammatory and NETs biomarkers were measured by ELISA (Enzyme Linked Immunosorbent Assay). NET formation was quantified by confocal microscopy. Neutrophil adhesion onto a human extracellular matrix (hECM) was assessed by optical microscopy. We recruited 22 healthy volunteers (HVs) and 18 patients with T2D. LDN counts in patients with diabetes were significantly higher (160%), along with circulating NETs biomarkers (citrullinated H3 histone (H3Cit), myeloperoxidase (MPO), and MPO-DNA (137%, 175%, and 69%, respectively) versus HV. Circulating interleukins (IL-6 and IL-8) and C-Reactive Protein (CRP) were significantly increased by 117%, 171%, and 79%, respectively, in patients compared to HVs. Isolated LDNs from patients expressed more H3Cit, MPO, and NETs, formed more NETs, and adhered more on hECM compared to LDNs from HVs. Patients with T2D present higher levels of circulating LDN- and NET-related biomarkers and associated pro-inflammatory activities.
AbstractList Type 2 diabetes (T2D) is characterized by low-grade inflammation. Low-density neutrophils (LDNs) represent normally less than 2% of total neutrophils but increase in multiple pathologies, releasing inflammatory cytokines and neutrophil extracellular traps (NETs). We assessed the count and role of high-density neutrophils (HDNs), LDNs, and NET-related activities in patients with T2D. HDNs and LDNs were purified by fluorescence-activated cell sorting (FACS) and counted by flow cytometry. Circulating inflammatory and NETs biomarkers were measured by ELISA (Enzyme Linked Immunosorbent Assay). NET formation was quantified by confocal microscopy. Neutrophil adhesion onto a human extracellular matrix (hECM) was assessed by optical microscopy. We recruited 22 healthy volunteers (HVs) and 18 patients with T2D. LDN counts in patients with diabetes were significantly higher (160%), along with circulating NETs biomarkers (citrullinated H3 histone (H3Cit), myeloperoxidase (MPO), and MPO-DNA (137%, 175%, and 69%, respectively) versus HV. Circulating interleukins (IL-6 and IL-8) and C-Reactive Protein (CRP) were significantly increased by 117%, 171%, and 79%, respectively, in patients compared to HVs. Isolated LDNs from patients expressed more H3Cit, MPO, and NETs, formed more NETs, and adhered more on hECM compared to LDNs from HVs. Patients with T2D present higher levels of circulating LDN- and NET-related biomarkers and associated pro-inflammatory activities.
Type 2 diabetes (T2D) is characterized by low-grade inflammation. Low-density neutrophils (LDNs) represent normally less than 2% of total neutrophils but increase in multiple pathologies, releasing inflammatory cytokines and neutrophil extracellular traps (NETs). We assessed the count and role of high-density neutrophils (HDNs), LDNs, and NET-related activities in patients with T2D. HDNs and LDNs were purified by fluorescence-activated cell sorting (FACS) and counted by flow cytometry. Circulating inflammatory and NETs biomarkers were measured by ELISA (Enzyme Linked Immunosorbent Assay). NET formation was quantified by confocal microscopy. Neutrophil adhesion onto a human extracellular matrix (hECM) was assessed by optical microscopy. We recruited 22 healthy volunteers (HVs) and 18 patients with T2D. LDN counts in patients with diabetes were significantly higher (160%), along with circulating NETs biomarkers (citrullinated H3 histone (H3Cit), myeloperoxidase (MPO), and MPO-DNA (137%, 175%, and 69%, respectively) versus HV. Circulating interleukins (IL-6 and IL-8) and C-Reactive Protein (CRP) were significantly increased by 117%, 171%, and 79%, respectively, in patients compared to HVs. Isolated LDNs from patients expressed more H3Cit, MPO, and NETs, formed more NETs, and adhered more on hECM compared to LDNs from HVs. Patients with T2D present higher levels of circulating LDN- and NET-related biomarkers and associated pro-inflammatory activities.Type 2 diabetes (T2D) is characterized by low-grade inflammation. Low-density neutrophils (LDNs) represent normally less than 2% of total neutrophils but increase in multiple pathologies, releasing inflammatory cytokines and neutrophil extracellular traps (NETs). We assessed the count and role of high-density neutrophils (HDNs), LDNs, and NET-related activities in patients with T2D. HDNs and LDNs were purified by fluorescence-activated cell sorting (FACS) and counted by flow cytometry. Circulating inflammatory and NETs biomarkers were measured by ELISA (Enzyme Linked Immunosorbent Assay). NET formation was quantified by confocal microscopy. Neutrophil adhesion onto a human extracellular matrix (hECM) was assessed by optical microscopy. We recruited 22 healthy volunteers (HVs) and 18 patients with T2D. LDN counts in patients with diabetes were significantly higher (160%), along with circulating NETs biomarkers (citrullinated H3 histone (H3Cit), myeloperoxidase (MPO), and MPO-DNA (137%, 175%, and 69%, respectively) versus HV. Circulating interleukins (IL-6 and IL-8) and C-Reactive Protein (CRP) were significantly increased by 117%, 171%, and 79%, respectively, in patients compared to HVs. Isolated LDNs from patients expressed more H3Cit, MPO, and NETs, formed more NETs, and adhered more on hECM compared to LDNs from HVs. Patients with T2D present higher levels of circulating LDN- and NET-related biomarkers and associated pro-inflammatory activities.
Audience Academic
Author Charles, Elcha
Sirois, Martin G.
Tardif, Jean-Claude
Villeneuve, Louis
Räkel, Agnès
White, Michel
Dumont, Benjamin L.
Neagoe, Paul-Eduard
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/38338951$$D View this record in MEDLINE/PubMed
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Snippet Type 2 diabetes (T2D) is characterized by low-grade inflammation. Low-density neutrophils (LDNs) represent normally less than 2% of total neutrophils but...
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SubjectTerms Biomarkers
C-reactive protein
Chronic illnesses
Cytokines
Diabetes
Diabetics
Disease
Enzyme-linked immunosorbent assay
Enzymes
Expenditures
Flow cytometry
Inflammation
Interleukins
Lymphocytes
Neutrophils
Type 2 diabetes
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Title Low-Density Neutrophils Contribute to Subclinical Inflammation in Patients with Type 2 Diabetes
URI https://www.ncbi.nlm.nih.gov/pubmed/38338951
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Volume 25
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