Rat alpha 2 macroglobulin is a selective inhibitor of antigen-induced leucotrienes in rat isolated lungs.
Exogenously administered, purified rat alpha 2 macroglobulin (alpha 2M, recognized as an acute phase reactant with anti-inflammatory properties) greatly inhibits the increase of the pulmonary resistance during the antigen-induced bronchoconstriction in rats in vivo, whereas a BaSO4 pretreatment (a method to induce a broad spectrum of serum acute phase reactants, including alpha 2M) covers a broader bronchoprotection: suppression of the decrease of the dynamic lung compliance as well. To explain these differences we studied the influence of both alpha 2M and BaSO4 on the antigen-induced bronchoconstriction in rat isolated lungs in relation to the mediator release in lung-effluents. We report here that in this model alpha 2M only inhibits the antigen-induced SRS-A release, whereas the concomitant release of histamine and 5-HT was unaffected. As distinct from alpha 2M the BaSO4 pretreatment suppressed both the antigen-induced bronchoconstriction and the histamine, 5-HT and SRS-A release to a high extent. These data suggest that alpha 2M can be considered as a selective inhibitor of leucotrienes, which offers an explanation for several anti-inflammatory properties of alpha 2M, including protection against the antigen-induced increase of the pulmonary resistance in vivo.
Ufkes
J G
JG
Department of Pharmacology, University of Amsterdam, The Netherlands.
Ottenhof
M
M
van Rooij
H H
HH
van Gool
J
J
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000941:Antigens / Q000276:immunology; D001466:Barium Sulfate / Q000494:pharmacology; D001681:Biological Assay; D001980:Bronchi / Q000187:drug effects; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology*; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D013189:SRS-A / Q000037:antagonists & inhibitors*; D012701:Serotonin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000494:pharmacology*
D000941:Antigens; D013189:SRS-A; D000511:alpha-Macroglobulins; D001466:Barium Sulfate; D012701:Serotonin