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Granulocyte-macrophage colony-stimulating factor (GM-CSF) but not granulocyte colony-stimulating factor (G-CSF) induces plasma membrane expression of proteinase 3 (PR3) on neutrophils in vitro
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Hellmich B Csernok E Trabandt A Gross WL Ernst M 《Clinical and experimental immunology》2000,120(2):392-398
The theoretical risk of triggering vasculitis resulting from administration of G-CSF and GM-CSF to patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), such as Wegener's granulomatosis (WG), who develop agranulocytosis due to cytotoxic therapy, is unknown. Since there is strong evidence that activation of polymorphonuclear neutrophils (PMN) induced by binding of ANCA to PR3 or myeloperoxidase (MPO) expressed on their plasma membrane is involved in the pathogenesis of systemic vasculitides (SV), we studied the surface expression of PR3 and MPO on PMN from healthy donors in response to G-CSF and GM-CSF in vitro by flow cytometric analysis. Increasing doses of G-CSF did not alter PR3 expression on either untreated or tumour necrosis factor-alpha (TNF-alpha)-primed donor PMN significantly. In contrast, GM-CSF significantly increased PR3 membrane expression on both intact PMN and neutrophils primed with TNF-alpha. MPO expression was not significantly altered by either G-CSF or GM-CSF. In summary, these data demonstrate that GM-CSF, but not G-CSF, induces plasma membrane expression of PR3 on PMN in vitro. Since in AAV accessibility of the antigen (PR3 or MPO) to the antibody (ANCA) on the plasma membrane of PMN is thought to be essential for neutrophil activation by ANCA, the results of the present study suggest that administration of GM-CSF to patients with WG with neutropenia implies a definite theoretical risk of deterioration of vasculitis via this mechanism. 相似文献
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Polymyalgia rheumatica (PMR) is a chronic inflammatory disorder of unknown etiology which typically presents with symmetric myalgias in the shoulder and pelvic girdles. Other clinical signs include the rapid onset of symptoms and the almost exclusive manifestation in the elderly population. In around 20% of cases, PMR is associated with giant cell arteritis (GCA). However, new imaging techniques suggest that the prevalence of subclinical GCA (e. g. aortitis) in PMR is probably higher. Acute phase reactants like erythrocyte sedimentation rate and c-reactive protein are usually elevated. Myalgias are accompanied by synovitis and bursitis of the large proximal joints and can be visualized by ultrasound or magnetic resonance imaging. While the diagnosis of GCA can be verified by temporal artery biopsy, pathognomonic findings for PMR like specific autoantibodies are lacking. Typical for PMR is the rapid response to corticosteroids. Usually the therapy needs to be continued for at least 2 years. Due to adverse events in many cases a corticosteroid saving therapy like methotrexate is needed. 相似文献
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Early detection of synovitis in rheumatoid arthritis (RA) and distinction from osteoarthritis (OA) are important to establish the most appropriate treatment. Increased perfusion over affected joints observed by laser Doppler perfusion imaging was supposed to arise from the underlying joint, because it was detected only by a near-infrared laser and not by a less penetrating red laser source. Using laser Doppler anemometry, this study addressed two questions: (1) whether capillary blood cell velocity (CBV) is increased in the skin over finger joints affected by RA or OA; (2) whether there is a difference between RA and OA in CBV above affected proximal interphalangeal (PIP) joints. Levels of soluble adhesion molecules were measured, because they indicate rheumatoid vasculitis raising flow resistance. Thirty-one patients with RA and 20 with OA were investigated. Compared to 18 controls, CBV (mean+/-SEM) was elevated above PIP joints clinically affected by RA (0.35+/-0.06 mm/s vs. 0.21+/-0.02 mm/s; P<0.05) and over PIP (0.27+/-0.02 mm/s vs. 0.21+/-0.02 mm/s; P<0.05) and distal interphalangeal joints (0.27+/-0.02 mm/s vs. 0.17+/-0.01 mm/s; P<0.001) affected by OA. Levels of soluble adhesion molecules were not correlated with CBV over PIP joints in RA. These observations demonstrated that elevated blood cell velocity is detectable by laser Doppler anemometry in skin capillaries over interphalangeal joints affected by RA or OA and contradict the previous assumption that there is hyperemia only in the affected joint. The lack of a significant difference in CBV over PIP joints between RA and OA patients might be due to some inflammation also occurring in OA rather than to vasculitic processes in RA associated with elevated levels of soluble adhesion molecules. 相似文献
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