ABSTRACT
Objective To investigate the pathogenesis of the production of anti-neutrophil cytoplasmic antibodies (ANCA) in the rat models of chronic bronchitis (CB) with recurrent infections. Methods The CB models were made by double element of smoking and lipopolysaccharide (LPS) stimulation. The rats were divided into four groups, including normal control group (n=5), phorbol-12-myristate-13-acetate (PMA)-treated healthy rats control group (n=5), CB rats group (n=5) and PMA-treated CB rats group (n=6). Renal function of rats was detected. The histopathological lung and kidney tissues were observed by HE staining of paraffin section. Immunological markers, including myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA), proteinase 3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA) and citrullinated histone H3 (CitH3), were measured by enzyme-linked immune-sorbent assay (ELISA) at different time points. Correlation between CitH3 and MPO-ANCA was analyzed by the Spearman rank correlation. NETs components were further detected in lung and kidney tissue by confocal immunofluorescence and colocalization analysis. Results (1) The serum levels of CitH3 and MPO-ANCA in CB+PMA group showed an increased trend. Compared with those in the normal control group and CB rats group, the serum levels of CitH3 and MPO-ANCA in CB+PMA group increased significantly at the sixth week (both P＜0.05). Serum CitH3 levels in rats were positively correlated with serum MPO-ANCA levels (rs=0.490,P=0.024). (2) There were pathological manifestations of CB in the lung tissues of rats in CB group and CB+PMA group, and no obvious abnormalities in the lung tissues of rats in the normal control group and control group. In the rat kidney tissue of CB+PMA group, there were inflammatory cells infiltrated in the glomerular and around the renal tubules, but glomerular necrosis was not found. No obvious abnormalities were observed in the kidney tissues of rats in the normal control group, PMA-treated healthy rats control group and CB group. (3) In the lung and kidney tissues of CB+PMA group NETs could be detected by confocal immunofluorescence analysis. Conclusion CB rats with the recurrent infections can release large amounts of NETs, in which the exposure of MPO antigen will break the immune tolerance and result in the production of MPO-ANCA.
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Objective To explore the significance of peptidylarginine deiminase type 4 (PAD4) in the pathogenesis of ANCA-associated vasculitis (AAV) by detecting its level in patients with AAV.Methods Sera from 13 patients with AAV,11 patients with primary chronic kidney disease and 12 healthy controls were collected.Serum PAD4 was detected using commercial ELISA kits.The association between serum PAD4 and BVAS of AAV was further investigated.Results (1) The serum level of PAD4 in patients with AAV in active and remission stages were all higher than that in the healthy controls.The serum level of PAD4 in patients with CKD was not found elevated compared with the normal controls.(2) The serum levels of PAD4 in AAV with renal damage were all significantly higher than that in CKD group no matter in active or remission stage.(3) The serum level of PAD4 in AAV with renal damage in active stage was positively correlated with BVAS (r=0.71,P=0.02).Conclusion PAD4 is involved in the pathogenesis of AAV.
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Objective To investigate the association of expressions of neutrophil extracellular trap (NET) and B lymphocyte in renal tissue with lupus activity in patients with lupus nephritis (LN). Methods Immunohistochemistry was.used to detect the expression of NET (citrullinated histone H3 as the marker) and the infiltration of B lymphocyte (CD19 as the marker)in renal specimens of three groups [LN group,n=20; minimal change disease (MCD) group,n=8;healthy control group,n=3].The chronic index and SLE-disease activity index (SLE-DAI) in renal tissues of LN and their correlations with NET and B lymphocytes were examined. Results The expression of NET was not found in the renal tissues of healthy control group and MCD group,while it increased significantly in LN group,especially in glomeruli with moderate and severe mesangial cells proliferation, cellular crescents, and tubulointerstitium with inflammatory cell infiltration.Compared with other types of glomeruli,the expression of NET was significantly upregulated in glomeruli with moderate and severe mesangial cell proliferation (P＜0.01).In the glomeruli with moderate and severe glomerular mesangial cell proliferation,the mean number of =NET positive cells was positively correlated with renal pathological active index (r=0.620,P=0.004),the score of SLE-DAI (r=0.492,P=0.027) and the mean number of NET positive tubular cells (r=0.558,P=0.011).In renal interstitium,the NET positive cells were positively correlated with CD19 positive B lymphocytes (r=0.573,P=0.008) and renal pathological chronic index (r=0.645,P=0.002). Conclusion NET is widely expressed in the renal tissues of lupus nephritis,which may play a role in the active damage of glomeruli.
ABSTRACT
To reveal the involvement of oxidative stress in hypertension and insulin resistance. Angiotensin Ⅱ was given to adrenomedullin-knockout mice for 4 weeks. 4-Hydroxy-TEMPOL, a superoxide scavenger mimetic was also employed. The results suggested that adrenomedullin may exert a protective effect against insulin resistance via its intrinsic antioxidant effect.