The in vitro effect of stone-wool has been studied in primary cultures of pulmonary alveolar macrophages (AM) and type II pneumocytes (T2) by morphological, biochemical and immunological methods. UICC crocidolite was applied as a positive control. Although stone-wool brought about frustrated phagocytosis, it did not induce serious membrane damage, whereas crocidolite gave rise to very severe membrane alterations. Stone-wool significantly reduced the activity of Cu,Zn/superoxide dismutase (SOD) in alveolar macrophages and significantly decreased the activity of gamma-glutamyl transpeptidase (GGT) in pneumocytes type II. Crocidolite, on the other hand, decreased the activity of all enzymes (glutathione peroxidase - GSH-Px, glutathione reductase - GSH-Rd) of glutathione metabolism in alveolar macrophages. It decreased the activity of all enzymes in pneumocytes type II except for Cu,Zn/SOD. After exposure to stone-wool, the production of inflammatory proteins, macrophage chemoattractant protein-1 (MCP-1) and macrophage inhibitory protein-1alpha (MIP-1alpha) increased in both cultured cells but did not reach the level induced by crocidolite. Although this study provided a useful insight in the toxicity of the stone-wool, we can not draw the conclusions how the intact pulmonary tissue may respond on the exposure to these fibres, exclusively based on the in vitro tests.
Heterogeneity and multifactoriality complicate diagnostics and our understanding of pathogenesis of rheumatoid arthritis (RA).The only accepted serologic parameter (rheumatoid factor [RF]) is not disease specific, nor are any of several novel RA autoantibodies.We aimed at identifying profiles instead of individual autoreactivities allowing for unambiguous prediction of RA.Selected RA autoantigens were tested by ELISA (RF and anti-cyclic citrullinated peptide [anti-CCP]) or Western blot (heavy-chain-binding protein [BiP], heterogeneous ribonucleoprotein particle A2 [RA33/ hnRNP A2], calpastatin and calreticulin).Antibody reactivities were assayed from serum samples of 149 RA patients and 132 patients with other rheumatic diseases and from synovial fluids (SF) (58 RA, 65 non-RA).No single autoreactivity was sufficient for unambiguous prediction of RA.Frequencies of multiparameter profiles consisting of 3, 4, 5 and 6 autoreactivites were determined.Fifteen six-parameter serum profiles were exclusively expressed in RA patients, representing a cumulative sensitivity of 59%.Twelve SF profiles were exclusively expressed in 64% of RA patients.The self-learning classification algorithm CLASSIF1 was capable of accurately predicting RA when these profiles were present.Data profile analysis of RF/CCP/BiP/calpastatin/calreticulin/RA33 provided specific discrimination of 64% of RA.Most importantly, RA specific profiles were observed in 64% of patients with early disease (<12 months).For the first time, the accurate prediction of the class RA has been achieved by the use of multiparametric autoreactivity profiles.Because of early expression in disease, these profiles make it possible to start a disease-modifying therapy long before irreversible bone and joint destruction may develop.Additional RA-specific profiles are required to cover the entire group of RA patients.
The influence of histamine (and the related agonists and antagonists) alone or in the presence of recombinant human interleukin 1α (IL‐1α) and gamma interferon (IFN‐γ) was studied on the production of complement components C3, C2, factor B, and C4 in vitro with human monocytoid cell line U937, hepatoma‐derived cell line HepG2, and mouse hepatocytes. Both U937 and HepG2 cells responded to histamine through H 1 and H 2 histamine receptors. The effect of histamine on the biosynthesis and gene expression of complement proteins was predominantly enhancing via the H 1 histamine receptors and inhibitory through the H 2 receptors. The actual predominance of the histamine receptor involved (and the outcome of the ligand interaction) seemed to be greatly affected by the simultaneous activation of the cells by IL‐1 or IFN‐γ.
We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA).An indirect immunofluorescence test and rat oesophagus substrate was used for the detection and quantification of AKA antibodies in patients´ sera.Overall 33/60 patients with JIA had sera positive for AKA (55 %, P = 0,0001) ranging from 1:10 to 1:160 dilutions.Following idiopathic arthritis of childhood classification criteria AKA occurred in 2/7 patients with systemic disease (28,6 %), in 13/30 patients with RF negative polyarthritis (43,3 %, P = 0,008) and in 15/18 RF positive polyarthritis (83,3 %, P = 0,000002).AKA were also found in a small cohort of patients with oligoarthritis (1/3) and psoriatic arthritis (2/2).AKA positivity occurred in 3/26 healthy controls at a 1:20 dilution.The presence of AKA was correlated as well as with the severity of the disease.Our study revealed that AKA was present overall in 18/29 patients (62%) with severe JIA and in 12/26 patients (46,2 %) with non-severe disease, however this did not reach statistical significance (P = 0,18).We also observed that AKA remained positive regardless of disease activity.AKA were detectable in 55,6 % patients with active JIA and in 48,6 % patients in the complete or near remission.
