Effect of macrophage depletion by liposomes containing dichloromethylene-diphosphonate on endotoxin-induced uveitis.
Footpad injection of lipopolysaccharide (LPS) from Salmonella typhimurium in Lewis rats induces an acute anterior and posterior endotoxin-induced uveitis (EIU). To investigate the role of macrophages in the pathogenesis of EIU, we eliminated macrophages by means of liposomes containing dichloromethylene-diphosphonate (Cl2MDP), a drug which depletes macrophages but not other immunocompetent cells. Intravenous injection of CL2MDP-liposomes clearly inhibited clinical and histological manifestations of uveitis in the anterior segment of the eye (iris/ciliary body) and reduced TNF level in aqueous humor. Specific immunostaining showed that CL2MDP-liposome injections decreased the number of ED2 + resident macrophages in the iris/ciliary body and the choroid. After LPS injection, CL2MDP-liposome treatment reduced the density of infiltrating ED1 + cells (mainly monocytes/macrophages) in the iris/ciliary body but not in the choroid; little or no effect was detected on the OX42 + cellular infiltration (mainly polymorphonuclear leukocytes). The inflammatory cellular infiltration of the retina was not modified by the treatment. These findings suggest that macrophages play a key role in the pathogenesis of ocular inflammation.
Pouvreau
I
I
Laboratoire d'Immunopathologie de l'Oeil, INSERM U86, Paris, France.
Zech
J C
JC
Thillaye-Goldenberg
B
B
Naud
M C
MC
Van Rooijen
N
N
de Kozak
Y
Y
D018712:Analgesics, Non-Narcotic; D000818:Animals; D000911:Antibodies, Monoclonal; D001082:Aqueous Humor / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002829:Choroid / Q000166:cytology / Q000276:immunology; D002924:Ciliary Body / Q000166:cytology / Q000276:immunology; D004002:Clodronic Acid; D007498:Iris / Q000166:cytology / Q000276:immunology; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008081:Liposomes / Q000737:chemistry; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D011506:Proteins / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D017463:Receptors, Complement 3b / Q000032:analysis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000209:etiology / Q000276:immunology*
D018712:Analgesics, Non-Narcotic; D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D008081:Liposomes; D011506:Proteins; D017463:Receptors, Complement 3b; D014409:Tumor Necrosis Factor-alpha; D004002:Clodronic Acid