PMID- 37365039 OWN - NLM STAT- MEDLINE DCOM- 20240108 LR - 20240108 IS - 1440-1592 (Electronic) IS - 1323-8930 (Linking) VI - 73 IP - 1 DP - 2024 Jan TI - Contribution of monocyte and macrophage extracellular traps to neutrophilic airway inflammation in severe asthma. PG - 81-93 LID - S1323-8930(23)00068-0 [pii] LID - 10.1016/j.alit.2023.06.004 [doi] AB - BACKGROUND: Increased blood/sputum neutrophil counts are related to poor clinical outcomes of severe asthma (SA), where we hypothesized that classical monocytes (CMs)/CM-derived macrophages (Mphi) are involved. We aimed to elucidate the mechanisms of how CMs/Mphi induce the activation of neutrophils/innate lymphoid cells (ILCs) in SA. METHODS: Serum levels of monocyte chemoattractant protein-1 (MCP-1) and soluble suppression of tumorigenicity 2 (sST2) were measured from 39 patients with SA and 98 those with nonsevere asthma (NSA). CMs/Mphi were isolated from patients with SA (n = 19) and those with NSA (n = 18) and treated with LPS/interferon-gamma. Monocyte/M1Mphi extracellular traps (MoETs/M1ETs) were evaluated by western blotting, immunofluorescence, and PicoGreen assay. The effects of MoETs/M1ETs on neutrophils, airway epithelial cells (AECs), ILC1, and ILC3 were assessed in vitro and in vivo. RESULTS: The SA group had significantly higher CM counts with increased migration as well as higher levels of serum MCP-1/sST2 than the NSA group. Moreover, the SA group had significantly greater production of MoETs/M1ETs (from CMs/M1Mphi) than the NSA group. The levels of MoETs/M1ETs were positively correlated with blood neutrophils and serum levels of MCP-1/sST2, but negatively correlated with FEV(1)%. In vitro/in vivo studies demonstrated that MoETs/M1ETs could activate AECs, neutrophils, ILC1, and ILC3 by increased migration as well as proinflammatory cytokine production. CONCLUSIONS: CM/Mphi-derived MoETs/M1ETs could contribute to asthma severity by enhancing neutrophilic airway inflammation in SA, where modulating CMs/Mphi may be a potential therapeutic option. CI - Copyright (c) 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved. FAU - Quoc, Quang Luu AU - Quoc QL AD - Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea; Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, South Korea. FAU - Cao, Thi Bich Tra AU - Cao TBT AD - Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea; Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, South Korea. FAU - Moon, Ji-Young AU - Moon JY AD - Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea. FAU - Jang, Jae-Hyuk AU - Jang JH AD - Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea. FAU - Shin, Yoo Seob AU - Shin YS AD - Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea. FAU - Choi, Youngwoo AU - Choi Y AD - Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea. FAU - Ryu, Min Sook AU - Ryu MS AD - Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea. FAU - Park, Hae-Sim AU - Park HS AD - Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea; Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, South Korea. Electronic address: hspark@ajou.ac.kr. LA - eng PT - Journal Article DEP - 20230624 PL - England TA - Allergol Int JT - Allergology international : official journal of the Japanese Society of Allergology JID - 9616296 SB - IM MH - Humans MH - *Extracellular Traps MH - Monocytes MH - Immunity, Innate MH - Lymphocytes MH - Neutrophils MH - *Asthma MH - Inflammation MH - Macrophages OTO - NOTNLM OT - Asthma OT - Macrophages OT - Monocytes OT - Neutrophils OT - Severe asthma EDAT- 2023/06/27 01:06 MHDA- 2024/01/08 06:42 CRDT- 2023/06/26 21:52 PHST- 2022/11/17 00:00 [received] PHST- 2023/04/29 00:00 [revised] PHST- 2023/05/16 00:00 [accepted] PHST- 2024/01/08 06:42 [medline] PHST- 2023/06/27 01:06 [pubmed] PHST- 2023/06/26 21:52 [entrez] AID - S1323-8930(23)00068-0 [pii] AID - 10.1016/j.alit.2023.06.004 [doi] PST - ppublish SO - Allergol Int. 2024 Jan;73(1):81-93. doi: 10.1016/j.alit.2023.06.004. Epub 2023 Jun 24.