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Research article1989Peer reviewed

A prothrombinase complex of mouse peritoneal macrophages

Lindahl, Ulf; Pejler, Gunnar; Bogwald, Jarl; Seljelid, Rolf

Abstract

Addition of prothrombin to mouse peritoneal macrophagesin vitroresulted in the formation of a thrombin-like enzyme, as demonstrated by use of the luminogenic peptide substrate S-2621. The prothrombinase activity was sedimented by high-speed centrifugation following homogenization of the cells and was abolished by treatment of the cells with the nonionic detergent Triton X-100 at 0.02% concentration. Moreover, the activity was drastically reduced by maintaining cultures in the presence of warfarin and, presumably due to competitive substrate inhibition, by adding S-2222, a chromogenic peptide substrate for Factor Xa. These findings suggest that prothrombin cleavage is catalyzed by Factor Xaat the macrophage surface. The generated thrombin was inhibited by antithrombin, and this reaction was accelerated by heparin with high affinity for antithrombin but not by the corresponding oligosaccharides composed of 8–14 monosaccharide units. Such oligosaccharides which are capable of accelerating the inactivation of Factor Xaby antithrombin, inhibited thrombin formation from prothrombin in the macrophage cultures, presumably by promoting inactivation by antithrombin of Factor Xain a prothrombinase complex. Activation of the macrophage coagulation system, as proposed to occur in certain inflammatory conditions, thus may be modulated at various levels by heparin, or heparin oligosaccharides, released from mast cells.

Published in

Archives of Biochemistry and Biophysics
1989, Volume: 273, number: 1, pages: 180-188
Publisher: ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS

      SLU Authors

    • Lindahl, Ulf

      • Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences

      • Pejler, Gunnar

        • Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences

      UKÄ Subject classification

      Immunology in the medical area
      Cell and Molecular Biology

      Publication identifier

      DOI: https://doi.org/10.1016/0003-9861(89)90177-X

      Permanent link to this page (URI)

      https://res.slu.se/id/publ/52778