Skip to main content
British Journal of Experimental Pathology logoLink to British Journal of Experimental Pathology
. 1988 Aug;69(4):457–464.

Rat alpha 2 macroglobulin is a selective inhibitor of antigen-induced leucotrienes in rat isolated lungs.

J G Ufkes 1, M Ottenhof 1, H H van Rooij 1, J van Gool 1
PMCID: PMC2013241  PMID: 2460121

Abstract

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.

Full text

PDF
457

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Carnuccio R., Di Rosa M., Flower R. J., Pinto A. The inhibition by hydrocortisone of prostaglandin biosynthesis in rat peritoneal leucocytes is correlated with intracellular macrocortin levels. Br J Pharmacol. 1981 Oct;74(2):322–324. doi: 10.1111/j.1476-5381.1981.tb09974.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Flower R. J., Blackwell G. J. Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. Nature. 1979 Mar 29;278(5703):456–459. doi: 10.1038/278456a0. [DOI] [PubMed] [Google Scholar]
  3. Gehring M. R., Shiels B. R., Northemann W., de Bruijn M. H., Kan C. C., Chain A. C., Noonan D. J., Fey G. H. Sequence of rat liver alpha 2-macroglobulin and acute phase control of its messenger RNA. J Biol Chem. 1987 Jan 5;262(1):446–454. [PubMed] [Google Scholar]
  4. Lewis D. A. Endogenous anti-inflammatory factors. Biochem Pharmacol. 1984 Jun 1;33(11):1705–1714. doi: 10.1016/0006-2952(84)90337-x. [DOI] [PubMed] [Google Scholar]
  5. Lewis R. A., Austen K. F., Drazen J. M., Clark D. A., Marfat A., Corey E. J. Slow reacting substances of anaphylaxis: identification of leukotrienes C-1 and D from human and rat sources. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3710–3714. doi: 10.1073/pnas.77.6.3710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Peters S. P., Siegel M. I., Kagey-Sobotka A., Lichtenstein L. M. Lipoxygenase products modulate histamine release in human basophils. Nature. 1981 Jul 30;292(5822):455–457. doi: 10.1038/292455a0. [DOI] [PubMed] [Google Scholar]
  7. Ufkes J. G., Ottenhof M., Labruyère W. T., Boers W., van Vugt H., van Gool J. The effects of alpha M-foetoprotein, an acute phase protein, and BaSO4-induced injury on IgE-mediated, systemic anaphylaxis in the rat. Br J Exp Pathol. 1986 Jun;67(3):321–327. [PMC free article] [PubMed] [Google Scholar]
  8. Vane J. R. The release and fate of vaso-active hormones in the circulation. Br J Pharmacol. 1969 Feb;35(2):209–242. doi: 10.1111/j.1476-5381.1969.tb07982.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Watts D. J. Protein synthesis during development and differentiation in the cellular slime mould Dictyostelium discoideum. Biochem J. 1984 May 15;220(1):1–14. doi: 10.1042/bj2200001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. van Gool J., Boers W., de Nie I. Inhibitory effects of rat alpha2 macroferoprotein (alphaMFP), an acute phase globulin, on galactosamine hepatitis. Exp Mol Pathol. 1978 Oct;29(2):228–240. doi: 10.1016/0014-4800(78)90041-2. [DOI] [PubMed] [Google Scholar]

Articles from British journal of experimental pathology are provided here courtesy of Wiley

RESOURCES