The Role of Macrophages in the Pathogenesis of Severe Asthma
- 주제(키워드) Asthma , autoimmunity , epithelial cells , extracellular traps , innate lymphoid cells , macrophages , monocytes , neutrophils , severe asthma
- 주제(DDC) 570
- 발행기관 아주대학교
- 지도교수 Hae-Sim Park
- 발행년도 2023
- 학위수여년월 2023. 8
- 학위명 박사
- 학과 및 전공 일반대학원 생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000032825
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
목차
CHAPTER Ⅰ 1
Contribution of monocyte and macrophage extracellular traps to neutrophilic airway inflammation in severe asthma 1
I. INTRODUCTION 2
II. MATERIALS AND METHODS 4
A. Materials 4
B. Study subjects 4
C. Protocol for isolation of immune cells 5
D. Human Mφ subset induction 9
E. The treatment protocols of human CMs and Mφ ex vivo 9
F. The treatment protocols of human blood neutrophils and AECs 10
G. The treatment protocols of human and mouse ILCs 11
H. Immunofluorescence assay 11
I. Migration, ROS, and apoptosis assays 12
J. Mouse experiments 12
K. Statistical analysis 14
III. RESULTS 15
A. Higher serum MCP-1 levels in patients with SA 15
B. Increased MoETs/M1ETs in the patients with SA 20
C. Signaling pathways of MoETs/M1ETs releases 28
D. The effects of MoETs/M1ETs on neutrophil activation in SA 33
E. The effects of MoETs/M1ETs on AECs in vitro 38
F. The effects of MoETs/M1ETs on human ILC activation 41
G. In vivo experiments in mice 45
H. The effects of MoETs/M1ETs in vivo 50
IV. DISCUSSION 55
CHAPTER II 62
Association between cytokeratin 19-specific IgG and neutrophil activation in asthma 62
I. INTRODUCTION 63
II. MATERIALS AND METHODS 65
A. Materials 65
B. Establishment of in vivo mouse models 65
C. Mouse ELISA 66
D. Lung tissue protein analysis 66
E. Lung neutrophil isolation and treatment in vivo 67
F. Study subjects and clinical parameters 67
G. Human ELISA for detecting serum CK19-IgG 68
H. Immunoblotting analysis 68
I. Immune cell isolation and ET formation 69
J. IgG and IC preparation 69
K. Evaluation of neutrophil activation 70
L. AEC culture and stimulation 70
M. Statistical analysis 71
III. RESULTS 72
A. MoET-induced CK19/CK19-specific IgG production in vivo 72
B. The effects of CD16/CD16.2 on neutrophilic inflammation in NA 72
C. Comparison of serum CK19-IgG level between EA and NEA 80
D. Circulating IgG involved in neutrophil degranulation 87
E. IC-induced NET formation mediated by CD16 receptor 93
F. Autocrine functions of ICs on monocyte activation in vitro 96
IV. DISCUSSION 99
CONCLUSIONS 105
