Trimellitic anhydride-induced allergic response in the lung: role of the complement system in cellular changes.
Trimellitic anhydride (TMA) is a small molecular weight industrial compound that will cause asthma-like symptoms in humans. Some of these TMA-induced symptoms can be reproduced in the guinea pig. In the guinea pig model of TMA-induced asthma, intratracheal instillation of TMA coupled to guinea pig serum albumin causes an immediate bronchoconstriction and increase in airway microvascular leakage with concomitant decrease in circulating platelets and white blood cells and subsequent cellular infiltration of mononuclear cells, neutrophils and eosinophils into the bronchoalveolar lavage fluid. In addition, in the lung tissue an increase in eosinophil peroxidase activity (a measure of eosinophil numbers) occurs. The purpose of this study was to determine whether complement system activation was essential for any of these TMA-induced events. Guinea pigs pretreated with cobra venom factor (CVF) had significantly reduced amounts of complement component C3 in the lavage fluid 24 hours after TMA conjugated to guinea pig serum albumin challenge indicating that the CVF treatment was successful in depleting complement proteins. Pretreatment with CVF did not affect the immediate TMA-induced bronchoconstriction nor the TMA-induced microvascular leakage. In animals depleted of the complement system by pretreatment with CVF the TMA-induced increase in mononuclear cells, total white blood cells, red blood cells, and EPO activity in the bronchoalveolar lavage was significantly reduced. Thus, our results suggest that in the guinea pig, the complement system is an important source of mediators for cellular infiltration into the lung after exposure to this acid anhydride and that inhibiting complement activation may be useful in preventing the inflammatory cell infiltration in TMA-induced asthma.
Fraser
D G
DG
Toxicology Graduate Program, University of Minnesota, Duluth, USA.
Regal
J F
JF
Arndt
M L
ML
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D003176:Complement C3 / Q000276:immunology*; D004342:Drug Hypersensitivity / Q000276:immunology*; D004347:Drug Interactions; D004546:Elapid Venoms / Q000494:pharmacology; D006168:Guinea Pigs; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010796:Phthalic Anhydrides / Q000276:immunology*
D000485:Allergens; D003176:Complement C3; D004546:Elapid Venoms; D010796:Phthalic Anhydrides; C016310:cobra venom factor; C015559:trimellitic anhydride