Influence of steric stabilization of liposome-encapsulated hemoglobin on Listeria monocytogenes host defense.
Liposome-encapsulated hemoglobin (LEH) products are being investigated as potential blood substitutes. To determine if changes in LEH composition can modify the immune response, red blood cell substitutes based on conventional lipids containing phosphatidylinositol (LEH1) and sterically stabilized lipid vesicles containing polyethylene glycol phosphatidylethanolamine (LEH2) were tested for effects on host resistance. On Day 0, groups of 18 to 20 female CD-1 mice were given an intravenous (i.v.) infectious challenge with a 20% lethal dose of Listeria monocytogenes. Mice received a single i.v. dose of LEH1, LEH2, or albumin vehicle on Day +1 or Day -3 relative to infectious challenge. Mice dosed with LEH1 and LEH2 on Day +1 died rapidly from Listeria infection; but mice dosed with LEH2 lived significantly longer than did mice receiving LEH1. By contrast, when administered on Day -3, LEH1 had no significant effect on host immunity, while LEH2 increased susceptibility to Listeria infection. In addition, LEH1 and LEH2 both caused significant reduction of phagocytic activity as measured by rat alveolar macrophage (AM) ingestion of latex microspheres. AM incubated 4 hr with either LEH1 or LEH2 prior to addition of microspheres ingested fewer beads in a dose-dependent manner. No difference in in vitro phagocytic activity was observed between LEH1 or LEH2. The inability to differentiate LEH formulations based on in vitro phagocytic activity suggests that the in vivo Listeria infection model may be more relevant in discerning the immunotoxicity of the LEH formulations tested.
Sherwood
R L
RL
IIT Research Institute, Life Sciences Department, Chicago, IL 60616, USA.
McCormick
D L
DL
Zheng
S
S
Beissinger
R L
RL
D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage* / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical; D005260:Female; D006207:Half-Life; D006454:Hemoglobins / Q000008:administration & dosage* / Q000737:chemistry; D007840:Latex; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D008089:Listeria monocytogenes / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000502:physiology; D008297:Male; D051379:Mice; D008863:Microspheres; D010587:Phagocytosis / Q000187:drug effects; D010713:Phosphatidylcholines / Q000737:chemistry / Q000633:toxicity; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000633:toxicity; D010716:Phosphatidylinositols / Q000737:chemistry / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry / Q000633:toxicity; D051381:Rats
D001802:Blood Substitutes; D006454:Hemoglobins; D007840:Latex; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols