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In vitro cleavage by asbestos fibers of the fifth component of human complement through free-radical generation and kallikrein activation.
No full textChrysotile and crocidolite fibers incubated in normal human plasma (NHP) generated from the C5 component of complement C5a-type fragments that stimulated polymorphonuclear leukocyte (PMN) chemotaxis. Absorption of NHP with antiserum against C5a totally abolished neutrophil chemotactic activity. Asbestos fibers also produced C5a small peptides in the presence of ethylene glycol bis(beta-aminoethyl ether) N,N,N'N'-tetraacetic acid (EGTA) but not ethylene diamine tetraacetic acid (EDTA). Activation of C5 was significantly inhibited when asbestos fibers were pretreated with iron chelators such as sodium dithionite (DTN), deferoxamine (DFX), or ascorbate (AA). Concentration-related inhibition of C5 activation was also observed when asbestos fibers were added concurrently to plasma in the presence of DFX, 1,3-dimethyl-2-thiourea (DMTU), a strong hydroxyl scavenger, or aprotinin (APR), a specific protease inhibitor. Further, chrysotile and crocidolite significantly increased plasma kallikrein activity. Data demonstrate that asbestos-induced C5 activation plays a role in inflammatory reactions characteristic of asbestosis through mechanisms involving iron ions, hydroxyl radicals, and oxidized C5-ike fragments. The ferrous ions present at the asbestos fiber surface trigger this activation and catalyze, via Fenton reaction, the production of hydroxyl radicals, which in turn convert native C5 to an oxidized C5-like form. This product is then cleaved by kallikrein, activated by the same asbestos fibers, yielding an oxidized C5a with the same functional properties as C5a
Wollastonite fibers in vitro generate reactive oxygen species able to lyse erythrocytes and activate the complement alternate pathway.
No full textRole of iron in asbestos-body-induced oxidant radical generation.
No full textAsbestos bodies (AB) were harvested from human lung tissue digests and isolated from uncoated asbestos fibers. Samples containing 1000 AB were added to a reactive solution to investigate the ability of AB to oxidize deoxy-D-ribose and generate reactive oxygen species (ROS) in the presence of ascorbate and hydrogen peroxide as determined by formation of thiobarbituric acid (TBA)-reactive products. Three types of asbestos fibers were tested for comparison, since they are known to be able to produce ROS. The absorbance values measured with 1000 AB were significantly higher than those observed with 1000 fibers of the three types of asbestos. Since in our reaction system the only source of transition metals was the iron-rich AB, data suggest iron derived from the ferritin coating of AB was involved in oxidant generation. Addition of iron to AB enhanced TBA-reactive product formation, while chelation of Fe with deferoxamine reduced this reaction. Hydroxyl radical scavengers 1,3-dimethyl-2-thiourea (DMTU) and mannitol (MN) also effectively blocked TBA-reactive product generation. Data indicate the importance of Fe in AB-induced oxidant damage. With the addition of polymorphonuclear leukocytes (PMN) to AB, incubation in the reactive solution gave very high amounts of TBA-reactive products, but using a reactive solution devoid of ascorbate, very low amounts of TBA-reactive products were generated. In the latter condition, the superoxide of cell membranes probably reduced and removed iron from AB-coating ferritin, but less effectively than ascorbate. Further after the possible reoxidation of Fe2+, Fe3+ could be coordinated by lactoferrin. Since such availability of reductant is never approached in living systems, the iron in the AB coating is unlikely to function as a catalyst of Fenton-type reactions in vivo
Reactive oxigen species measured from suspensions of polymorphonuclear leucocytes after addiction of silicon carbide particles.
No full textAbstract: A sample of silicon carbide (SiC) dust was collected from a factory manufacturing SiC abrasives, then tested in vitro to find out whether it could produce reactive oxygen species (ROS) after its addition to human polymorphonuclear leukocyte suspensions. We compared the results of milled and unmilled SiC with those obtained from quartz dust and asbestos fibres, which are known causes of severe pulmonary lesions. ROS production was measured with the chemiluminescence (CL) technique. CL values obtained with our two forms of SiC (milled and unmilled) were approximately twice those measured in the controls (where no mineral particles were added), approximately 80% of the values found with asbestos fibres, and only 12.5% of the values measured with quartz. Iron traces were found on the surface of a small number of the particles tested, which could be as a result of contamination. These iron traces could help to explain our findings, since, together with the iron traces present in the culture medium, they could have triggered ROS generation in a Fenton-type reaction
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