elastin and Arthritis--Rheumatoid

Elastases are proteinases capable of solubilizing fibrous elastin. They may belong to the class of serine proteinases, cysteine proteinases and metalloproteinases. Mammalian elastases occur mainly in the pancreas and the phagocytes. Among non-mammalian elastases there is a great variety of bacterial metallo and serine elastases. The elastolytic activity varies from one elastase to another and is usually not correlated with the catalytic efficiency of these proteinases. One may measure this activity using native or labelled elastins. With pure elastases one may use synthetic substrates. There is a large number of natural (proteins) and synthetic elastase inhibitors. Elastases play a pathologic role in pulmonary emphysema, cystic fibrosis, infections, inflammation and atherosclerosis.

Topics: alpha 1-Antitrypsin Deficiency; alpha-Macroglobulins; Animals; Arteriosclerosis; Arthritis, Rheumatoid; Bacterial Proteins; Catalysis; Cathepsin G; Cathepsins; Elastin; Enzyme Inhibitors; Fibroblasts; Glycosaminoglycans; Humans; Leukocytes; Mammals; Organ Specificity; Pancreas; Pancreatic Elastase; Phagocytes; Polynucleotides; Pseudomonas Infections; Pulmonary Emphysema; Serine Endopeptidases; Species Specificity; Substrate Specificity

Vocal fold scarring remains a significant problem. Although several animal models have been developed to improve our understanding of the histopathology, the histologic features of scarred human vocal folds have rarely been reported. The present case studies aimed to define the histologic changes of scarred human vocal folds caused by cordectomy or cordotomy. Ten patients with the scarred vocal folds were involved in this study. Nine patients with early glottic cancer underwent endoscopic cordectomy, and one patient underwent superficial cordotomy for idiopathic scar. The postcordectomy or cordotomy scar was biopsied or resected 3-13 months after the original procedure. After confirming absence of any tumor in cancer patients, the remaining specimens were used in the present study. Histologic examination investigated deposition of extracellular matrix (ECM) including collagen, elastin, hyaluronic acid (HA), fibronectin, and decorin in the lamina propria of the scarred vocal folds. There was a wide range of variation in the deposition of ECM in scarred vocal folds. Excessive and disorganized collagen deposition was observed in most cases that had undergone deep resection of the lamina propria, whereas deposition of collagen was mild and well organized after superficial resection. Decorin was retained in all cases after superficial cordectomy or cordotomy, but varied after deep resection. Deposition of elastin, HA, and fibronectin varied regardless of depth of injury. Histology of scarred vocal folds may vary with degree of injury and individual healing mechanism.

Topics: Adult; Aged; Arthritis, Rheumatoid; Cicatrix; Collagen; Decorin; Elastin; Extracellular Matrix; Extracellular Matrix Proteins; Female; Fibronectins; Humans; Hyaluronic Acid; Immunohistochemistry; Laryngeal Neoplasms; Male; Middle Aged; Proteoglycans; Vocal Cords

In present study we investigated whether the serum concentration of tumour necrosis factor alpha (TNF-alpha) is associated with soluble adhesion molecules and vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA) patients. Serum levels of TNF-alpha, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble E-selectin (sE-selectin) and VEGF were assessed by ELISA in 38 patients with RA. We demonstrated the TNF-alpha to correlate with sICAM-1 (p < 0.001), sVCAM-1 (p < 0.01) and VEGF (p < 0.01). No association was noticed between TNF-alpha and sE-selectin serum concentrations. Moreover, serum TNF-alpha, sICAM-1, sVCAM-1 and VEGF levels correlated with markers of RA activity such as the erythrocyte sedimentation rate, C reactive protein level and the number of swollen joints. Data presented in this report support the concept of the VEGF synthesis stimulation by TNF-alpha. Analysis of the serum TNF-alpha, sICAM-1, sVCAM-1 and VEGF levels may be useful in the prediction of the RA activity.

Topics: Adult; Aged; Arthritis, Rheumatoid; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intercellular Adhesion Molecule-1; Male; Middle Aged; Predictive Value of Tests; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factor A

In this study, we evaluated the in vitro and in vivo potency of human leukocyte elastase (HLE) and human cathepsin G (HCG) as proteoglycanases. In vitro evaluation was done using bovine nasal septum aggrecan and aggrecan/hyaluronan aggregate as substrates. Enzyme activity was assessed by the ability of the proteinases to abrogate the ability of aggrecan to aggregate with hyaluronan. In vivo activity of the proteinases was tested by injecting purified HLE and HCG intra-articularly into rabbit stifle joints and quantifying the levels of proteoglycan released into synovial fluids. On a molar basis, HCG was at least tenfold more potent than HLE as a proteoglycanase in vitro. Moreover, HCG was twofold more potent as a proteoglycanase in vivo. In contrast, HLE hydrolyzed elastin approximately 22-fold faster than HCG, but was only slightly more rapid than HCG when [3H]-transferrin was used as substrate. These data indicate that HCG is more potent than HLE as a proteoglycanase both in vitro and in vivo. Thus, HCG could be more important in the pathogenesis of rheumatoid arthritis than previously suspected.

Topics: Aggrecans; Animals; Arthritis, Rheumatoid; Cartilage, Articular; Cathepsin G; Cathepsins; Cattle; Elastin; Extracellular Matrix Proteins; Female; Humans; Hyaluronic Acid; Injections, Intra-Arterial; Lectins, C-Type; Leukocyte Elastase; Pancreatic Elastase; Proteoglycans; Rabbits; Serine Endopeptidases; Synovial Fluid; Transfection; Tritium

Blood monocyte elastolytic activity in patients with rheumatoid arthritis and in normal controls was studied by a new in vitro technique. The enzyme activity of live cells was measured by soluble [3H]elastin hydrolysis first under basic conditions and then after immune complex stimulation. The cells from patients had a higher elastolytic potential than cells from controls (p less than 0.02) and responded to smaller amounts of immune complex (p less than 0.01), even in patients treated with D-penicillamine or aurothiomalate. Treatment of normal monocytes in vitro with aurothiomalate did not influence the elastolytic response. These findings indicate that monocytes from patients with rheumatoid arthritis have an enhanced elastolytic activity compared with cells from normal controls and may invoke greater tissue damage on immune complex stimulation.

Topics: Adult; Aged; Aged, 80 and over; Antigen-Antibody Complex; Arthritis, Rheumatoid; Cells, Cultured; Elastin; Female; Gold Sodium Thiomalate; Humans; Male; Middle Aged; Monocytes; Pancreatic Elastase; Penicillamine

In order to further investigate the role of the immune system in the arteriosclerotic process, we investigated the anti-elastin peptide antibodies (AEAb) of the IgG and IgM types by DOT immunobinding assay in the sera of patients suffering from various arteriosclerotic diseases. In total 232 control and pathological sera were studied. In obliterative arteriosclerosis of the legs 90%, ischemic heart disease 67% and hypertension 60% of sera were positive for AEAb of the IgG type independent of age. In the case of diabetes mellitus, however, the duration of the disease was determinant. In rheumatoid arthritis, the results were negative. No clear-cut positivity could be demonstrated in stroke patients either. These results indicate that AEAb can be detected in some diseases and DOT appears to be an appropriate method for the AEAb screening in various diseases.

Topics: Adult; Age Factors; Aged; Arteriosclerosis; Arthritis, Rheumatoid; Coronary Disease; Diabetes Mellitus; Elastin; Female; Humans; Hypertension; Immunoglobulin G; Immunoglobulin M; Immunosorbent Techniques; Male; Middle Aged; Peptide Fragments

Topics: Adolescent; Adult; Aged; Antigen-Antibody Complex; Arthritis, Juvenile; Arthritis, Rheumatoid; Collagen; Connective Tissue; Elastin; Female; Glycosaminoglycans; Humans; Hydroxyproline; Immune Complex Diseases; Male; Middle Aged

Rheumatoid arthritis can be divided into two syndromes, one a potassium deficiency, the other an inappropriate copper requirement seriously affecting the elastin tissues through reduced lysyl oxidase cross linking. The malfunction in copper may arise from the steroids which regulate potassium, which reduces those steroids, and through that, increases the copper response to the needs of the immune system. It is a mechanism which may have evolved to help fight potassium wasting infections.

Topics: Animals; Arthritis, Rheumatoid; Ceruloplasmin; Copper; Corticosterone; Elastin; Female; Humans; Hydrocortisone; Immune System; Male; Potassium Deficiency; Protein-Lysine 6-Oxidase; Rats

The cells of the connective tissues contain lysosomes with enzymes capable of degrading intercellular substances (collagen, elastin, proteoglycans) and release their enzymes in membrane-bound or in free form into their intercellular substance. In this way extracellularly located lysosomes (= matrix lysosomes) can be detected by morphological and enzymatic means as well as by their metal concentrating property. This function of such matrix-lysosomes is in connection with the two step-degradation of the connective tissue and is thought to be the main part for the fibrocytic fibrolysis, chondrocytic chondrolysis, osteocytic osteolysis and myocytic mediolyses in the vessel wall. The cells of the mesenchymal tissues thus control the turnover and transformation of their own ground substance. Inflammatory and immunologic processes are suggested to be superimposed on this lysosomal action. If the lysosomal enzyme system in the connective tissues and the vessel wall gets out of control, the consequences can be dangerous as e.g. in case of relapsing polychondritis and arterial aneurysms. In this enzyme system proteolytic activators as well as proteolytic decomposable inhibitors are present. The corresponding proteolytic processes are of lysosomal nature and are subordinated to other regulatory mechanisms.

Topics: Aneurysm; Animals; Arthritis, Rheumatoid; Collagen Diseases; Connective Tissue; Elastin; Female; Humans; Lysosomes; Male; Microscopy, Electron; Middle Aged; Polychondritis, Relapsing; Proteoglycans; Rats; Vascular Diseases

Topics: Arthritis, Rheumatoid; Cathepsins; Collagen; Connective Tissue; Elastin; Endopeptidases; Granulocytes; Humans; Hydrogen-Ion Concentration; Joints; Kininogens; Lysosomes; Microbial Collagenase; Neutrophils; Pancreatic Elastase; Proteoglycans

Topics: Arthritis, Rheumatoid; Cartilage; Chymotrypsin; Elastin; Electrophoresis, Polyacrylamide Gel; Granulocytes; Histones; Humans; Hyaluronoglucosaminidase; Hydrogen-Ion Concentration; Hydrolysis; Leukocytes; Lymphocytes; Peptide Hydrolases; Potassium Chloride; Proteoglycans; Synovial Fluid

Topics: Antibodies; Arthritis, Rheumatoid; Collagen; Connective Tissue; Elastin; Glycoproteins; Glycosaminoglycans; Hemagglutination Tests; Humans; Immunodiffusion