Dissemination of beads coated with trehalose 6,6'-dimycolate: a possible role for coagulation in the dissemination process

Abstract

When spread as a monolayer on the surface of hydrophobic beads and injected into mice, the mycobacterial glycolipid, trehalose 6,6'-dimycolate, reproduces the biologic effects traditionally associated with virulent mycobacteria, including acute inflammation, granuloma formation, and immune adjuvancy. Repeated intraperitoneal injection of glycolipid-coated beads into young C57Bl/6 mice elicits a granulomatous peritonitis, with concomitant dissemination of beads from the peritoneum to distant organs. Glycolipid-coated beads which disseminate from the peritoneum to other sites elicit neither acute inflammation nor granulomata. The coagulation system may be involved in the dissemination of glycolipid-coated beads as evidenced by the following: fibrinogen is a necessary cofactor of the trehalose dimycolate monolayer; diffuse peritoneal and pulmonary hemorrhage accompanies bead dissemination; peritoneal exudate collected shortly after intraperitoneal injection of glycolipid-coated beads is enriched in coagulant activity; coagulability of blood from trehalose dimycolate-treated animals is reduced; and anticoagulation inhibits the inflammatory response to glycolipid-coated beads. In this report, the dissemination of trehalose dimycolate-coated beads is characterized, and a role for the coagulation system in this process is proposed.