Activation of complement by plicatic acid, the chemical compound responsible for asthma due to western red cedar (Thuja plicata).
Plicatic acid, a low-molecular-weight compound responsible for western red cedar (Thuja plicata) asthma was tested for its ability to activate complement and to generate chemotactic activity from pooled normal human serum (NHS). Dose-dependent complement consumption was found as determined by hemolytic assay (CH50). Activation of complement by plicatic acid was also confirmed by the demonstration of conversion of C3 to C3b on immunoelectrophoresis. This activation was completely prevented by pretreating the serum with either edetate (EDTA) or ethylene glycol tetraacetic acid (EGTA), suggesting that complement was activated via the classical pathway. No conversion of factor B was seen in any of the samples. Leukocyte chemotactic activity was also generated when serum was incubated with plicatic acid. The consumption of C3 and CH50 was unimpaired in two samples of serum from patients with severe, untreated hypogammaglobulinemia and thus appears to be immunoglobulin independent. These observations suggest that plicatic acid could activate complement in vivo, thereby inducing an inflammatory response in the airways and contributing to the higher prevalence of industrial chronic bronchitis in exposed subjects. The pathogenetic role of complement activation in red cedar asthma has yet to elucidated.
D000818:Animals; D001249:Asthma / Q000139:chemically induced*; D002264:Carboxylic Acids / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D007122:Immunoelectrophoresis; D017705:Lignans; D009284:Naphthols / Q000494:pharmacology*; D011817:Rabbits; D012756:Sheep; D014197:Trees / Q000276:immunology*; D015054:Zymosan / Q000494:pharmacology
D002264:Carboxylic Acids; D003176:Complement C3; D017705:Lignans; D009284:Naphthols; D004533:Egtazic Acid; D015054:Zymosan; D004492:Edetic Acid; C008938:plicatic acid