Vol. 29, pp.705 ~ 711, 2001 High mobility group 1 HMG1 13 12 20 anti-neutrophil cytoplasmic antibodies, ANCA ANCA 1982 Davies 1980 1 high mobility group HMG1 HMG2 30 kd high mobility group HMGHMG HMG1 HMG2 HMG1 HMG1 42 1 13 12 8 ANCA ANCA cytoplasmic; C-ANCA perinuclear; P-ANCA C- ANCA proteinase 3 PR3 PR3 Wegener P-ANCA myeloperoxidase MPO MPO pauci-immune PR3 MPO ELISA ANCA PR3 MPO double negative ANCA ANCA ANCA 1 HMG1/HMG2 47
1 1 P-ANCA HMG1 HMG2 35 ANCA 22 63% P-ANCA cathepsin G 7 lactoferrin 3 MPO P-ANCA lysate immunoblotting P-ANCA 10 58, 47, 44, 40, 28 kd 1 3 28 kd 7 HL-60 lysate immunoblotting 2 28 kd cathepsin G 6M guanidine/hcl HL-60 PBS HPLC 2 immunoblotting 29 kd 28 kd 2 SDS-PAGE Edman N 32 29 kd 28 kd HMG1 HMG2 P- ANCA 28/29 kd HMG1/HMG2 28/29 kd immunoblotting HMG1/HMG2 HMG1/HMG2 HL-60 28/29 kd immunoblotting 28 kd 29 kd immunoblotting 28/29 kd HMG1/HMG2 3 P-ANCA HMG1/HMG2 HMG1/HMG2 P- ANCA HMG1/HMG2 1 : 1 4 HMG1/HMG2 HMG1/HMG2 3 HMG1/HMG2 P-ANCA HMG1/HMG2 HMG1/HMG2 HMG1/HMG2 HMG1/HMG2 HMG1/HMG2 ELISA HMG1/HMG2 48
HMG1 2 HMG1/HMG2 % 5 6 7 2 HMG1 HMG2 1 HMG1 79% HMG2 86% 89% 2 P-ANCA HMG1 HMG2 P-ANCA HMG1/HMG2 HMG1/HMG2 70% P-ANCA 5 RA SLE Sjögren HMG1/HMG2 HMG1 HMG2 2 P-ANCA MPO, cathepsin G, lactoferrin, HMG1/HMG2 RA P-ANCA HMG1/HMG2 HMG1/HMG2 RA SLE HMG1/HMG2 6 HMG1/HMG2 RA P-ANCA RA SLE HMG1/HMG2 35% 2 P-ANCA 43% P-ANCA HMG1/HMG2 49
1 HMG1/HMG2 U/ml 7 2 HMG1/HMG2 14% 5/35 5 2 Sjögren 8 HMG1/HMG2 1 HMG1 HMG2 1 HMG1/HMG2 30 kd high mobility group HMGHMG HMG1, 2, 14, 17, I, Y HMG1 HMG2 214 208 25,000 HMG1/HMG2 HMG1 HMG2 80% 80 2 DNA 30 HMG1 50
HMG1 23 HMG2 2 DNA HMG A B 2 HMG A/B HMG1 DNA DNA HMG1 DNA HMG2 mrna HMG2 RNA antisense HMG2 HMG1/HMG2 DNA T B V D J 12/23 bp DNA HMG1 HMG2 9 2 amphoterin/hmg1 30 kd amphoterin HMG1 amphoterin/hmg1 mrna amphoterin/hmg1 amphoterin/hmg1 amphoterin/hmg1 amphoterin/hmg1 t-pa 10 N18 amphoterin/hmg1 t-pa t-pa amphoterin/hmg1 amphoterin/hmg1 t-pa 11 3 amphoterin/hmg1 murine erythroleukemia; MEL hexamethylene bisacetamide HMBA MEL 29 kd HMBA MEL cdna amphoterin/hmg1 12 HMBA HMG1 MEL HMG1 TNF-α 13 HMG1 14 HMG1 HMG1 HMG1 15 HMG1 fibroblast growth factor FGF interleukin-1, transglutaminase, ciliary neurotrophic factor, lactose-binding lectin L-14 exocytosis 16 HMG1 HMG1 10 ng/ml n=24 HMG1 DIC/MOF 36 34 6 HMG1 HMG1 24 13~15 HMG1 51
4 amphoterin/hmg1 amphoterin/hmg1 RAGE RAGE advanced glycation end products AGEs RAGE AGEs RAGE Hori RAGE 12 kd 23 kd amphoterin/hmg1 17 amphoterin/hmg1 well RAGE RAGE RAGE amphoterin/hmg1 mrna RAGE amphoterin/hmg1 2 HMG1 trafficking HMG1 1 2 3 HMG1 t-pa P HMG1 RAGE HMG1 HMG1 5 HMG1 HMG1 HMG2 3 1 2 3 t-pa RAGE HMG1 HMG1 2 HMG1 HMG1 HMG1 2 1 1.. 1998; 53 (3 ): 564-572. 2 Sobajima J, et al. Anti-neutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis: anti-cathepsin G and a novel antobody correlate with a refractory type. Clin Exp Immunol 1996; 105: 120-124. 3 Sobajima J, et al. Novel autoantigens of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) in ulcerative colitis: non-histone chromosomal proteins, HMG1 and HMG2. Clin Exp Immunol 1997; 107: 135-140. 52
HMG1 4 Uesugi H, et al. High mobility group non-histone chromosomal proteins HMG1 and HMG2: Are they P-ANCA target antigens? Clin Exp Immunol 1998; 112 (Suppl. 1): 52. 5 Sobajima J, et al. High mobility group (HMG) nonhistone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis. Gut 1999; 44: 867-873. 6 Uesugi H, et al. Prevalence and characterization of novel P-ANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic diseases. J Rheumatol 1998; 25: 703-709. 7 Sobajima J, et al: Prevalence and characterization of P-ANCA directed against HMG1 and HMG2 in ulcerative colitis. Clin Exp Immunol 1988; 111: 402-407. 8. High mobility group HMG1/ HMG2:. 1998; 21: 95-107. 9 Calogero S, et al. The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice. Nat Genet 1999; 22: 276-280. 10 Parkkinen J, et al. Interactions of plasminogen and tissue plasminogen activator (t-pa) with amphoterin. J Biol Chem 1991; 266: 16730-16735. 11 Parkkinen J, et al. Amphoterin, the 30-kDa protein in a family of HMG1-type polypeptides. J Biol Chem 1993; 268: 19726-19738. 12 Melloni E, et al. Identity in molecualr structure between "differentiation enhancing factor" of murine erythroleukemia cells and the 30kD heparin-binding protein of developing rat brain. Biochem Biophys Res Commun 1995; 210: 82-89. 13 Wang H, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999; 285: 248-251. 14 Ombrellino M, et al. Increased serum concentrations of high-mobility-group protein 1 in haemorrhagic shock. Lancet 1999; 354: 1446-1447. 15 Abraham E, et al. HMG-1 as a mediator of acute lung inflammation. J Immunol 2000; 165: 2950-2954. 16 Cooper DNW, et al. Evidence for export of a muscle lectin from cytosol to extracellular matrix and for a novel secretory mechanism. J Cell Biol 1990; 110: 1681-1691. 17 Hori O, et al. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. J Biol Chem 1995; 270: 25752-25761. 53