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Titolo:
Neutrophil priming and apoptosis in anti-neutrophil cytoplasmic autoantibody-associated vasculitis
Autore:
Harper, L; Cockwell, P; Adu, D; Savage, COS;
Indirizzi:
Univ Birmingham, Sch Med, MRC, Div Med Sci,Ctr Immune Regulat, Birmingham B15 2TT, W Midlands, England Univ Birmingham Birmingham W Midlands EnglandB15 2TT W Midlands, England
Titolo Testata:
KIDNEY INTERNATIONAL
fascicolo: 5, volume: 59, anno: 2001,
pagine: 1729 - 1738
SICI:
0085-2538(200105)59:5<1729:NPAAIA>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROGRAMMED CELL-DEATH; VITRONECTIN RECEPTOR; IN-VITRO; WEGENERS GRANULOMATOSIS; RECOGNITION MECHANISM; SYSTEMIC VASCULITIS; AGING NEUTROPHILS; SUPEROXIDE ANION; MACROPHAGES; PHAGOCYTOSIS;
Keywords:
anti-neutrophil cytoplasmic antibodies; superoxide; apoptosis; inflammatory response; small vessel vasculitis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Savage, COS Univ Birmingham, Sch Med, MRC, Div Med Sci,Ctr Immune Regulat,Birmingham B15 2TT, W Midlands, England Univ Birmingham Birmingham W Midlands England B15 2TT England
Citazione:
L. Harper et al., "Neutrophil priming and apoptosis in anti-neutrophil cytoplasmic autoantibody-associated vasculitis", KIDNEY INT, 59(5), 2001, pp. 1729-1738

Abstract

Background. Interactions between anti-neutrophil cytoplasmic autoantibody (ANCA) and primed neutrophils (PMNs) may be central to the pathogenesis of primary small vessel vasculitis. PMNs from patients are primed, expressing proteinase 3 (PR3) on the cell surface, which permits interaction with ANCA. In vitro ANCA activates primed PMN to degranulate and generate a respiratory burst. Resultant reactive oxygen species are important in triggering apoptosis, but the fate of PMN in ANCA-associated vasculitis is unknown. Failure to remove apoptotic PMN in a nonphlogistic manner may sustain the inflammatory response. Methods. PMNs from patients or controls were isolated, and the basal production of superoxide was measured by the superoxide dismutase-inhibitable I eduction of ferricytochrome C. ANCA antigen expression on apoptotic PMN wasassessed at 0, 12, and 18 hours by flow cytometry using dual staining withFITC-conjugated annexin V and PE-conjugated anti-murine IgG against monoclonal ANCA. Apoptosis was also assessed by morphology. In further studies, apoptotic PMNs were opsonized with monoclonal anti-myeloperoxidase (MPO) or anti-proteinase-3 (PR3) or irrelevant isotype-matched IgG (N IgG) and phagocytosis by macrophages was measured using interaction assays. Cytokines interleukin-8 (IL-8) and interleukin-1 were measured by enzyme-linked immunosorbent assay (ELISA). Results. Proteinase-3 expression (active 63.0 +/- 5.6% of total number of cells, remission 51.47 +/- 7.9% of total number of cells, control 17.7 +/-:3.74b of total number of cells, P < 0.05) and basal superoxide production (active 6.9 +/- 0.8 nmol/L x 10(6) cells, remission 5.15 +/- 0.4 nmol/L/10(6) cells, control 3.63 +/- 0.3 nmol/L/10(6) cells, P < 0.001) were significantly greater with freshly isolated PMN from patients than controls. PR3 expression and superoxide generation were positively correlated. PMN from patients with active disease became apoptotic at a greater rate than those of controls (at 18 hours, patients 72.3 +/- 3.9% apoptosis, controls 53.2 +/-:2.7% apoptosis, P < 0.05). PR3 and MPO expression were significantly greater on PMN isolated from patients at 12 and 18 hours. Opsonization of apoptotic PMN with ANCA significantly enhanced recognition and phagocytosis by scavenger macrophages (anti-MPO 88.95 +/- 6.27, anti-PR3 93.93 +/- 4.90, N IgG 44.89 +/- 3.44, P < 0.01) with increased secretion of IL-1 (anti-PR3 34.73 +/- 6.8 pg/mL, anti-MPO 32.01 +/- 12.3 pg/mL, N IgG 8.04 +/- 6.3 pg/mL, P< 0.05) and IL-8 (anti-PR3 8.97 +/- 0.93 ng/mL, anti-MPG 8.45 +/- 1.46 ng/mL, N IgG 0.96 +/- 0.15 ng/ml, P < 0.01). Conclusion. In vivo circulating PMNs are primed as assessed by PR3 expression and basal superoxide production, thereby enhancing their inflammatory potential. These PMNs undergo apoptosis more readily, at which times they express PR3 and MPO on their surface. These antigens may then provide targetsfor ANCA. Opsonization of apoptotic PMN will enhance clearance by macrophages but will also trigger the release of proinflammatory cytokines that maycontribute to chronic inflammation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 09:32:52