Local inflammation in axial spondyloarthritis (axSpA) leads to the release of collagen metabolites from the disease-affected tissue. We investigated whether collagen metabolites were associated with disease activity and could distinguish non-radiographic(nr)-axSpA from ankylosing spondylitis (AS). A total of 193 axSpA patients (nr-axSpA, n = 121 and AS, n = 72) and asymptomatic controls (n = 100) were included. Serum levels of metalloproteinase (MMP)-degraded collagen type I (C1M), type II (C2M), type III (C3M) and type IV (C4M2) were quantified by enzyme-linked immunosorbent assay (ELISA). All metabolites were higher in axSpA than in controls (all p < 0.001). Serum levels of C1M, C3M, and C4M2 were increased in AS compared to nr-axSpA (43.4 ng/mL vs. 34.6; p < 0.001, 15.4 vs. 12.8; p = 0.001, and 27.8 vs. 22.4; p < 0.001). The best metabolite to differentiate between axSpA and controls was C3M (AUC 0.95; specificity 92.0, sensitivity 83.4). C1M correlated with ASDAS-CRP in nr-axSpA (ρ = 0.37; p < 0.001) and AS (ρ = 0.57; p < 0.001). C1M, C3M, and C4M2 were associated with ASDAS-CRP in AS and nr-axSpA after adjustment for age, gender, and disease duration. Serum levels of collagen metabolites were significantly higher in AS and nr-axSpA than in controls. Moreover, the present study indicates that collagen metabolites reflect disease activity and are useful biomarkers of axSpA.

• MeSH
• ankylózující spondylitida krev   diagnóza   MeSH
• biologické markery krev   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• fibrilární kolageny metabolismus   MeSH
• kolagen typ II metabolismus   MeSH
• kolagen typ III metabolismus   MeSH
• kolagen typu I metabolismus   MeSH
• kolagen typu IV metabolismus   MeSH
• lidé MeSH
• spondylartritida krev   diagnóza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• fibrilární kolageny MeSH
• kolagen typ II MeSH
• kolagen typ III MeSH
• kolagen typu I MeSH
• kolagen typu IV MeSH

Hypoxia can cause basement membrane (BM) degradation in tissues. Matrix metalloproteinase 9 (MMP-9) is involved in various human cancers as well as BM degradation by downregulating type IV collagen (COL4). This study investigated the role of MMP-9 in hypoxia-mediated BM degradation in rat bone marrow based on its regulation of collagen type IV alpha 1 chain (COL4A1). Eighty male rats were randomly divided into four groups based on exposure to hypoxic conditions at a simulated altitude of 7,000 m, control (normoxia) and 3, 7, and 10 days of hypoxia exposure. BM degradation in bone marrow was determined by transmission electron microscopy. MMP-9 levels were assessed by western blot and real-time PCR, and COL4A1 levels were assessed by western blot and immunohistochemistry. Microvessels BMs in bone marrow exposed to acute hypoxia were observed by electron microscopy. MMP-9 expression increased, COL4A1 protein expression decreased, and BM degradation occurred in the 10-, 7-, and 3-day hypoxia groups compared with that in the control group (all P < 0.05). Hypoxia increased MMP-9 levels, which in turn downregulated COL4A1, thereby increasing BM degradation. MMP-9 upregulation significantly promoted BM degradation and COL4A1 downregulation. Our results suggest that MMP-9 is related to acute hypoxia-induced BM degradation in bone marrow by regulating COL4A1.

• MeSH
• bazální membrána * metabolismus   MeSH
• hypoxie metabolismus   MeSH
• kolagen typu IV * metabolismus   MeSH
• krysa rodu Rattus MeSH
• matrixová metaloproteinasa 9 * metabolismus   MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kolagen typu IV * MeSH
• matrixová metaloproteinasa 9 * MeSH
• Mmp9 protein, rat MeSH Prohlížeč

The expression of all six chains of collagen IV was studied using the indirect fluorescent immunohistochemistry in seven control corneas and seven corneas obtained from patients suffering from the posterior polymorphous corneal dystrophy. Heterogeneous staining, especially in the epithelial basement membrane and Descemet's membrane, was observed in the control corneas. An increase of the staining intensity for the alpha1 and alpha2 chains was observed, especially in the Descemet's membrane and the corneal stroma in samples obtained from the patients compared to the control tissues.

• MeSH
• dědičné dystrofie rohovky metabolismus   MeSH
• Descemetova membrána chemie   MeSH
• dospělí MeSH
• fluorescenční protilátková technika nepřímá MeSH
• kolagen typu IV analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rohovka chemie   MeSH
• stroma rohovky chemie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• kolagen typu IV MeSH

Posterior polymorphous corneal dystrophy (PPCD) is a hereditary bilateral disorder affecting primarily the endothelium and Descemet's membrane (DM). The aim of this study was to determine the changes in the presence and localization of the alpha1-alpha6 collagen IV chains and alpha1, alpha2 collagen VIII chains in Czech patients with PPCD. Twelve corneal buttons from ten PPCD patients who underwent corneal grafting, as well as eight unaffected corneas, were used. Enzymatic indirect immunohistochemistry was performed on cryosections using antibodies against the alpha1-alpha6 collagen IV chains and alpha1, alpha2 collagen VIII chains. The intensity of the signal was examined separately in the basal membrane of the epithelium (BME), stroma and DM. More than 50% of PPCD specimens exhibited positivity for alpha1 and alpha2 collagen IV chains in the BME and in the posterior stroma, while no staining was detected in these areas in control specimens. The signal for the alpha1 and alpha2 collagen IV chains was more intense in DM of PPCD corneas compared to controls and it was shifted from the stromal side (in control tissue) to the endothelial side of DM (in the patients). A less intensive signal in PPCD corneas for the alpha3 and alpha5 chains in DM and an accumulation of alpha3-alpha5 in the posterior stroma in diseased corneas were the only differences in staining for the alpha3-alpha6 collagen IV chains. The alpha1 collagen VIII chain was detected on both the endothelial and the stromal sides of DM in 90% of patients with PPCD, compared with the prevailing localization on the stromal side of DM in control corneas. A change in the localization of the alpha2 collagen VIII chain in DM from vertically striated features in control specimens to double line positivity in the DM of PPCD corneas and positive staining in the posterior collagenous layer of four patients were also detected. In three PPCD patients a fibrous pannus located under the BME, positive for alpha1-alpha3, alpha5 collagen IV chains and alpha1 collagen VIII chain, was observed. The increased expression of the alpha1, alpha2 collagen IV and alpha1 collagen VIII chains and the change in their localization in DM may contribute to the increased endothelial proliferative capacity observed in PPCD patients.

• MeSH
• bazální membrána metabolismus   patologie   MeSH
• Bowmanova membrána metabolismus   patologie   MeSH
• dědičné dystrofie rohovky metabolismus   patologie   MeSH
• dospělí MeSH
• imunoenzymatické techniky MeSH
• kolagen typ VIII metabolismus   MeSH
• kolagen typu IV metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• rohovka metabolismus   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kolagen typ VIII MeSH
• kolagen typu IV MeSH

BACKGROUND: In the pathogenesis of dermatitis herpetiformis the participation of some proteins of the extracellular matrix has not been elucidated so far. They are found more amply in the papillary derma where they are manifested most markedly as the mentioned type of dermatosis. The objective of the present work was to assess the participation of components of the extracellular matrix in the pathogenesis of diseases and the possibility of their detection to make a more accurate diagnosis. METHODS AND RESULTS: In a group of 11 patients (mean age 39 +/- 17 years) with dermatitis herpetiformis the diagnosis was established on the basis of the clinical and histological finding. Fibronectin and collagens type I, III, IV, V were assessed in the skin using rabbit antisera (INPHARM Co. Moscow). An elevated level of collagen type III and V was found in the affected papillae and on the floor of the blisters in the papillary derma, collagen type IV on the vault of the blister and fibronectin deposits in the affected papillae which had a netlike structure. CONCLUSIONS: Based on the above findings assessment of fibronectin, collagens type III, IV and V in the affected skin can be considered an important supplementary examination in the histological diagnosis of dermatitis herpetiformis.

• MeSH
• dermatitis herpetiformis metabolismus   MeSH
• dospělí MeSH
• fibronektiny analýza   MeSH
• kolagen analýza   MeSH
• kůže chemie   MeSH
• lidé MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• fibronektiny MeSH
• kolagen MeSH

Spontaneous regression (SR) of human melanoma is a rare, well-documented phenomenon that is not still fully understood. Its detailed study cannot be performed in patients due to ethical reasons. Using the Melanoma-bearing Libechov Minipig (MeLiM) animals of various ages (from 3 weeks to 8 months) we implemented a long-term monitoring of melanoma growth and SR. We focused on immunohistochemical detection of two important extracellular matrix proteins, collagen IV and laminin, which are associated with cancer. We showed that SR of melanoma is a highly dynamic process. The expression of collagen IV and laminin correlated with changes in population of melanoma cells. Tumours of 3-week-old animals consisted primarily of melanoma cells with a granular expression of collagen IV and laminin around them. Thereafter, melanoma cells were gradually destroyed and tumour tissue was rebuilt into the connective tissue. Collagen IV expression slightly increased in tumours of 10-week-old pigs showing extracellular fibrous appearance. In tumours of older animals, areas lacking melanoma cells demonstrated a low expression and areas still containing melanoma cells a high expression of both proteins. We considered the age of 10 weeks as a turning point in the transition between tumour growth and SR of the MeLiM melanoma.

• Klíčová slova
• MeLiM, collagen IV, laminin, porcine melanoma, spontaneous regression,
• Publikační typ
• časopisecké články MeSH

Primary cutaneous desmoplastic melanoma (DM) is a group of rare melanocytic tumors arising on severely sun-damaged skin, histologically characterized by the proliferation of spindled melanocytes in a prominent desmoplastic stroma, with a range of morphological presentations. In this article, we report a unique case of primary cutaneous DM composed of a nodular proliferation of highly pleomorphic spindled and epithelioid cells, pseudoglandular structures, clear cell change, and unusual collagen rosettes. Immunohistochemical analysis showed a strong and diffuse positivity for S-100 protein, SOX-10, nestin, p75 (nerve growth factor receptor), WT1, and p53. Molecular analysis detected a mutation in the NF1 gene [c.4084C > T, p.(Arg1362Ter)], 2 different pathogenic mutations in TP53 [c.742C > T, p.(Arg248Trp), AF:12%, COSM1640831 and c.528C > G, p.(Cys176Trp), AF:12%, COSM11114], and a mutation in GNAS [c.601C > T, p.(Arg201Cys), AF: 9%, COSM123397]. To the best of our knowledge, this is the first case reporting collagen rosettes and pseudoglandular features in primary cutaneous DM.

• MeSH
• chromograniny genetika   MeSH
• imunohistochemie MeSH
• kolagen typu IV metabolismus   MeSH
• lidé MeSH
• melanom genetika   metabolismus   patologie   MeSH
• mutace MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory kůže genetika   metabolismus   patologie   MeSH
• neurofibromin 1 genetika   MeSH
• proteiny vázající GTP - alfa-podjednotky Gs genetika   MeSH
• senioři nad 80 let MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• chromograniny MeSH
• GNAS protein, human MeSH Prohlížeč
• kolagen typu IV MeSH
• nádorový supresorový protein p53 MeSH
• neurofibromin 1 MeSH
• NF1 protein, human MeSH Prohlížeč
• proteiny vázající GTP - alfa-podjednotky Gs MeSH

Antibodies to collagen type I and III reacted negatively, antibodies to collagen type IV positively with reticulin, trabeculae and circumferent reticulum of lymphatic sheaths, poorly positively with capsula, strongly positively with subcapsular zone. Antibodies to collagen type II reacted positively with capsula, poorly with subcapsular zone, strongly with sinus wall and poorly with trabeculae. They did not react with circumferent reticulum of periarterial lymphoid sheaths. Antibodies to collagen type II and IV reacted positively with central arteries. Antibodies to chondroitinsulphate C reacted poorly and antibodies to chondroitinsulphate B strongly positively with sinus walls and oval cells spread in the white and red pulpa. Antibodies to chondroitin sulphate A reacted similarly as antibodies to chondroitinsulphate B.

• MeSH
• chondroitin sulfáty analýza   imunologie   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• kolagen analýza   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• protilátky MeSH
• slezina chemie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• chondroitin sulfáty MeSH
• kolagen MeSH
• protilátky MeSH

Proteinases secreted by an axenic strain of Trichomonas tenax were active against native types I, III, IV and V collagens when evaluated by polyacrylamide gel electrophoresis. Degradation of all four collagen types was temperature dependent. Basement membrane type IV collagen was digested most effectively. An inhibition of all collagenolytic activities by a specific inhibitor of cysteine proteinases, E-64, and activation by a reducing agent, dithiothreitol, indicated the involvement of cysteine proteinases of the oral flagellate in the cleavage of collagen.

• MeSH
• bazální membrána enzymologie   metabolismus   MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• endopeptidasy metabolismus   fyziologie   MeSH
• gnotobiologické modely MeSH
• kolagen klasifikace   metabolismus   MeSH
• lidé MeSH
• teplota MeSH
• Trichomonas enzymologie   MeSH
• ústní sliznice enzymologie   metabolismus   parazitologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• endopeptidasy MeSH
• kolagen MeSH

BACKGROUND: Myeloperoxidase (MPO) is an abundant hemoprotein expressed by neutrophil granulocytes that is recognized to play an important role in the development of vascular diseases. Upon degranulation from circulating neutrophil granulocytes, MPO binds to the surface of endothelial cells in an electrostatic-dependent manner and undergoes transcytotic migration to the underlying extracellular matrix (ECM). However, the mechanisms governing the binding of MPO to subendothelial ECM proteins, and whether this binding modulates its enzymatic functions are not well understood. METHODS: We investigated MPO binding to ECM derived from aortic endothelial cells, aortic smooth muscle cells, and fibroblasts, and to purified ECM proteins, and the modulation of these associations by glycosaminoglycans. The oxidizing and chlorinating potential of MPO upon binding to ECM proteins was tested. RESULTS: MPO binds to the ECM proteins collagen IV and fibronectin, and this association is enhanced by the pre-incubation of these proteins with glycosaminoglycans. Correspondingly, an excess of glycosaminoglycans in solution during incubation inhibits the binding of MPO to collagen IV and fibronectin. These observations were confirmed with cell-derived ECM. The oxidizing and chlorinating potential of MPO was preserved upon binding to collagen IV and fibronectin; even the potentiation of MPO activity in the presence of collagen IV and fibronectin was observed. CONCLUSIONS: Collectively, the data reveal that MPO binds to ECM proteins on the basis of electrostatic interactions, and MPO chlorinating and oxidizing activity is potentiated upon association with these proteins. GENERAL SIGNIFICANCE: Our findings provide new insights into the molecular mechanisms underlying the interaction of MPO with ECM proteins.

• Klíčová slova
• 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid, 3,3′,5,5′-tetramethylbenzidine, 5,5′-dithiobis(2-nitrobenzoic) acid, 5-thio-2-nitrobenzoic acid, ABTS, BAECs, BSA, CTAC, Cardiovascular disease, Collagen IV, DMF, DTNB, ECM, EDTA, ELISA, Endothelium, Enzyme activity, Fibronectin, GAGs, HRP, Inflammation, MCD, MPO, N,N-dimethylformamide, OD, PBS, RASMCs, RT, SEM, TMB, TNB, bovine aortic endothelial cells, bovine serum albumin, cetyltrimethylammonium chloride, enzyme-linked immunosorbent assay, ethylenediaminetetraacetic acid, extracellular matrix, glycosaminoglycans, horseradish peroxidase, monochlorodimedon, myeloperoxidase, optical density, phosphate buffered saline, rat aortic smooth muscle cells, room temperature, standard error of the mean,
• MeSH
• cévní endotel cytologie   metabolismus   MeSH
• dimerizace MeSH
• dusičnany metabolismus   MeSH
• extracelulární matrix - proteiny chemie   metabolismus   MeSH
• fibronektiny metabolismus   MeSH
• glykosaminoglykany metabolismus   MeSH
• kolagen typu IV metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• oxidační stres MeSH
• peroxidasa metabolismus   MeSH
• tyrosin metabolismus   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dusičnany MeSH
• extracelulární matrix - proteiny MeSH
• fibronektiny MeSH
• glykosaminoglykany MeSH
• kolagen typu IV MeSH
• peroxidasa MeSH
• tyrosin MeSH