Discordant effects on eicosanoids and fibrin degradation products in two murine models of antiphospholipid antibody.
Two murine models of lupus were employed to challenge an hypothesized mechanism by which antiphospholipid antibodies (APLA) might promote thrombosis: altering prostacyclin (PGI2) and thromboxane (TX) production. PGI2 levels in mouse blood and the ex vivo release of PGI2 and TX from mouse kidney were measured. Since APLA have been reported to alter synthesis or activation of several molecules mediating fibrinolysis, murine plasma levels of the fibrin degradation product, D-dimer were also determined. Two murine strains, one prone to spontaneous "lupus-like" illness (MRL-lpr) and related strain (MRL-(+2)), were compared. The assays confirm that MRL-lpr mice have increased anticardiolipin antibody (ACA) and two-fold increased release of TX from renal tissues compared to MRL-(+2) mice. However, these mice have low levels of plasma D-dimer. NIH Swiss mice injected with IgG (containing APLA) from thrombosis-prone lupus patients had high blood ACA titers and D-dimer levels, but both ACA and D-dimer were low or non-detectable in Swiss mice injected with saline or normal IgG. Unlike mice with spontaneous lupus-like illness, healthy mice injected with APLA did not differ from controls with respect to plasma or tissue PGI2 or TX levels. The two murine models of lupus differ, because an altered PGI2-TX ratio is a finding in the chronic murine lupus strain MRL-lpr, but is not seen when APLA are injected into normal mice. It is unlikely that APLA alone has a direct effect on cellular production of eicosanoids in vivo.
Schorer
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Department of Medicine, Minneapolis VA, MN, USA. schor007@maroon.tc.umn.edu
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis
D017152:Antibodies, Antiphospholipid; D015777:Eicosanoids; D005338:Fibrin Fibrinogen Degradation Products; D007074:Immunoglobulin G; D000001:Calcimycin; D013929:Thromboxane B2; D011464:Epoprostenol; D013917:Thrombin