Inhibition of immune complex-induced enteropathy by three different platelet-activating factor receptor antagonists.
We previously showed that intravenous injection of rat anti-BSA-BSA complexes (IC) prepared in 5x antigen excess rapidly induced a striate pattern of serosal (to mucosal) hemorrhage and vascular congestion throughout the small intestine of the Sprague-Dawley rat. In this study, we tested the effect of three different platelet-activating factor (PAF) receptor antagonists on the development of lesions. L-652,731, a synthetic derivative of kadsurenone (at doses of 1.3-2.7 mg/kg), SRI 63-675, a substituted quinolinium compound (6.7-15 mg/kg), and WEB 2086, a thienotriazolodiazepine (5-25 mg/kg) were each capable of completely or partially inhibiting IC-induced enteropathy in the majority of animals tested. Pretreatment with WEB 2086 prevented IC-induced hemoconcentration but not neutropenia. The antagonists did not lower the level of blood complement nor interfere with the fall in complement induced by administration of IC. The ability of PAF receptor antagonists to completely or partially inhibit IC-induced small intestinal lesions suggests that endogenous PAF is a major mediator of IC-induced enteropathy.
Bloch
K J
KJ
Department of Medicine, Harvard Medical School, Boston, MA.
Ng
B P
BP
Bishara
S M
SM
Bloch
M
M
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001381:Azepines / Q000627:therapeutic use; D005663:Furans / Q000627:therapeutic use; D007410:Intestinal Diseases / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D010980:Platelet Membrane Glycoproteins; D011804:Quinolines / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D043562:Receptors, G-Protein-Coupled; D012710:Serum Albumin, Bovine / Q000276:immunology; D014230:Triazoles / Q000627:therapeutic use
D000906:Antibodies; D000936:Antigen-Antibody Complex; D001381:Azepines; D005663:Furans; D010980:Platelet Membrane Glycoproteins; D011804:Quinolines; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; C053130:SRI 63-675; D012710:Serum Albumin, Bovine; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran