Biological effects of short-term, high-concentration exposure to methyl isocyanate. VI. In vitro and in vivo complement activation studies.
The ability of MIC to induce complement activation in vitro and in vivo was investigated. For the in vitro studies, both human and guinea pig serum or EDTA-plasma samples were exposed to 1167 to 1260 ppm MIC vapor for 15 min at room temperature. The human serum samples exposed to MIC showed significant reductions in Factor B, C2, C4, C3, C5, and total hemolytic complement CH50 activity levels. C6 functional activity was unaffected. The C3, C5, and CH50 functional activities in guinea pig serum (the only functional tests conducted on these samples) were more sensitive to MIC-mediated reduction than the corresponding activity reductions observed in the human serum samples. The human and single guinea pig EDTA-plasma samples exposed to MIC vapor showed no evidence of C3 consumption but did show significant reductions in CH50 levels. Thus, MIC vapor was able to activate, and thereby reduce serum complement C3 activity in vitro by a complement-dependent process. However, the data suggest at least one complement component other than C3 was inactivated in EDTA-plasma by a complement-independent mechanism. For the in vivo studies, five pairs of guinea pigs were exposed to 644 to 702 ppm MIC vapor until one of the pair died (11-15 min). MIC exposure was then discontinued, the surviving guinea pig was sacrificed, and EDTA-plasma was obtained from both animals and analyzed for complement consumption.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000378:metabolism; D003182:Complement C5 / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism; D003485:Cyanates / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D017953:Isocyanates
D003176:Complement C3; D003182:Complement C5; D003485:Cyanates; D017953:Isocyanates; D003165:Complement System Proteins; C008461:methyl isocyanate