Characterization of an anti-lymphocyte function-associated antigen-1 antibody in a simian immunodeficiency virus-pig-tailed macaque (Macaca nemestrina) model.
The simian immunodeficiency virus (SIV)/pig-tailed macaque (Macaca nemestrina) model of acquired immune deficiency syndrome (AIDS) is a powerful system in which to study cell adhesion molecules and retroviral pathogenesis in vivo. Preliminary experiments were conducted to examine the role of lymphocyte function-associated antigen 1 (LFA-1) in early SIV infection in vivo by using an LFA-1 monoclonal antibody (MHM.23) specific to human LFA-1. In vitro studies revealed that at concentrations of > or = 20 microg/ml, MHM.23 blocked LFA-1-mediated adhesion and T-cell activation (>90%) of pig-tailed macaque peripheral blood mononuclear cells (PBMCs). In addition, SIVmac239 infection of macaque cells was inhibited in a dose-dependant manner by MHM.23. Administration of MHM.23 to pig-tailed macaques inhibited LFA-1-ICAM-1-mediated activity in vivo and maintained binding on macaque cells for < or = 4 d. Our in vitro studies indicated that at an MHM.23 concentration of 20 microg/ml, macaque PBMCs were completely saturated. Our in vivo studies determined that 5 mg/kg MHM.23 intravenously every 24 h was required to maintain saturating levels and inhibit LFA-1-ICAM-1 function in pig-tailed macaques.
Fletcher
Craig A
CA
Department of Comparative Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. cfletch@jhmi.edu
Liao
Zhaohao
Z
Adams
Robert J
RJ
Carter
Darryl L
DL
Jones
Odell D
OD
Davis
Harry G
HG
Bryant
Joseph L
JL
Hildreth
James E K
JE
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000635:transmission; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics; D002448:Cell Adhesion; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008254:Macaca nemestrina; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000635:transmission; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity / Q000502:physiology*; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1