High mobility group 1 HMG1

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1 Vol. 29, pp.705 ~ 711, 2001 High mobility group 1 HMG anti-neutrophil cytoplasmic antibodies, ANCA ANCA 1982 Davies high mobility group HMG1 HMG2 30 kd high mobility group HMGHMG HMG1 HMG2 HMG1 HMG 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

2 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 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 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

3 HMG1 2 HMG1/HMG2 % 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

4 1 HMG1/HMG2 U/ml 7 2 HMG1/HMG2 14% 5/ Sjögren 8 HMG1/HMG2 1 HMG1 HMG2 1 HMG1/HMG2 30 kd high mobility group HMGHMG HMG1, 2, 14, 17, I, Y HMG1 HMG ,000 HMG1/HMG2 HMG1 HMG2 80% 80 2 DNA 30 HMG1 50

5 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 HMG1 HMG ~15 HMG1 51

6 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 HMG HMG1 t-pa P HMG1 RAGE HMG1 HMG1 5 HMG1 HMG1 HMG t-pa RAGE HMG1 HMG1 2 HMG1 HMG1 HMG ; 53 (3 ): 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: 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:

7 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): 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: 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: Sobajima J, et al: Prevalence and characterization of P-ANCA directed against HMG1 and HMG2 in ulcerative colitis. Clin Exp Immunol 1988; 111: High mobility group HMG1/ HMG2:. 1998; 21: 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: Parkkinen J, et al. Interactions of plasminogen and tissue plasminogen activator (t-pa) with amphoterin. J Biol Chem 1991; 266: Parkkinen J, et al. Amphoterin, the 30-kDa protein in a family of HMG1-type polypeptides. J Biol Chem 1993; 268: 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: Wang H, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999; 285: Ombrellino M, et al. Increased serum concentrations of high-mobility-group protein 1 in haemorrhagic shock. Lancet 1999; 354: Abraham E, et al. HMG-1 as a mediator of acute lung inflammation. J Immunol 2000; 165: 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: Hori O, et al. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. J Biol Chem 1995; 270: