Late treatment with anti-LFA-1 (CD11a) antibody prevents cerebral malaria in a mouse model.
CBA/Ca mice injected with Plasmodium berghei develop cerebral malaria (CM) characterized by ataxia and progressive paralysis leading to death 7-9 days after experimental infection. The development of cerebral symptoms is a function of the immune response in susceptible strains, and depends on cell-cell interactions involving T helper cells and mononuclear phagocytes. Here we ask whether antibodies to cell adhesion receptors of the immune system can influence the development of CM in this mouse model. When administrated on day 6 after infection, antibody to the leukocyte integrin leukocyte function-antigen-1 (LFA-1) but not antibodies to MAC-1, LECAM-1 (the MEL-14 antigen), alpha 4 integrin or ICAM-1 dramatically reduced the incidence of CM, leading to survival of most mice until the later onset of anemia. Anti-LFA-1 treatment did not result in a substantial decrease in the monocyte accumulation observed in cerebral vessels of susceptible mice. Its efficacy may be related to the broader roles of LFA-1 in cell-cell interactions important in the later pathogenic stages of the immune response to the parasite. Perturbation of immune cell function through interference with cell adhesion mechanisms may offer an important therapeutic tool in acute, life-threatening immune-mediated disorders.
Falanga
P B
PB
Department of Pathology, Stanford University Medical Center.
Butcher
E C
EC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001921:Brain / Q000469:parasitology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D004195:Disease Models, Animal; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000276:immunology; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008808:Mice, Inbred CBA; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010962:Plasmodium berghei
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1