INFLUENCE OF STERIC STABILIZATION OF LIPOSOME-ENCAPSULATED HEMOGLOBINON LISTERIA-MONOCYTOGENES HOST-DEFENSE

Liposome-encapsulated hemoglobin (LEH) products are being investigated as potential blood substitutes. To determine if changes in LEH compos ition can modify the immune response, red blood cell substitutes based on conventional lipids containing phosphatidylinositol (LEH1) and ste rically stabilized lipid vescicles containing polyethylene glycol phos phatidylethanolamine (LEH2) were tested for effects on host resistance . On Day 0, groups of 18 to 20 female CD-1 mice were given an intraven ous (i.v.) infectious challenge with a 20% lethal dose of Listeria mon ocytogenes. Mice received a single i.v. dose of LEH1, LEH2, or albumin vehicle on Day + 1 or Day -3 relative to infectious challenge. Mice d osed with LEH1 and LEH2 on Day + 1 died rapidly from Listeria infectio n; but mice dosed with LEH2 lived significantly longer than did mice r eceiving LEH1. By contrast, when administered on Day -3, LEH1 had no s ignificant effect on host immunity, while LEH2 increased susceptibilit y to Listeria infection. In addition, LEH1 and LEH2 both caused signif icant reduction of phagocytic activity as measured by rat alveolar mac rophage (AM) ingestion of latex microspheres. AM incubated 4 hr with e ither LEH1 or LEH2 prior to addition of microspheres ingested fewer be ads in a dose-dependent manner. No difference in in vitro phagocytic a ctivity was observed between LEH1 or LEH2. The inability to differenti ate LEH formulations based on in vitro phagocytic activity suggests th at the in vivo Listeria infection model may be more relevant in discer ning the immunotoxicity of the LEH formulations tested.