TY - JOUR
T1 - Effect of immune mechanisms on the pharmacokinetics and organ distribution of Cryptococcal polysaccharide
AU - Lendvai, Nikoletta
AU - Casadevall, Arturo
AU - Liang, Zhenglu
AU - Goldman, David L.
AU - Mukherjee, Jean
AU - Zuckier, Lionel
N1 - Funding Information:
Financial support: NIH (AI-22274 and AI-13342 to A.C. and J.M.; GM-07288 to N.L.; AI-01300 to D.L.G.); Burroughs Wellcome Developmental Therapeutics Award (A.C. and J.M.).
PY - 1998
Y1 - 1998
N2 - Cryptococcus neoformans is an encapsulated opportunistic fungus that can cause chronic infections accompanied by high tissue levels of capsular polysaccharide (CPS). CPS or its major component, glucuronoxylomannan (GXM), was administered to mice, and whole-body and tissue levels were measured. The role of monoclonal antibody (MAb), complement, and CD4 T cells in GXM clearance was also examined. These studies demonstrate that CPS is cleared from the blood within days but is retained in the body for weeks; that MAbs of all isotypes examined promote GXM clearance; that MAb-mediated GXM deposition in liver, but not in spleen, is Fc-dependent; that complement enhances IgM-mediated GXM sequestration in liver but not spleen; and that CD4 T cells are not necessary for serum GXM clearance. The results have important implications for the eventual use of MAbs in treatment of cryptococcosis.
AB - Cryptococcus neoformans is an encapsulated opportunistic fungus that can cause chronic infections accompanied by high tissue levels of capsular polysaccharide (CPS). CPS or its major component, glucuronoxylomannan (GXM), was administered to mice, and whole-body and tissue levels were measured. The role of monoclonal antibody (MAb), complement, and CD4 T cells in GXM clearance was also examined. These studies demonstrate that CPS is cleared from the blood within days but is retained in the body for weeks; that MAbs of all isotypes examined promote GXM clearance; that MAb-mediated GXM deposition in liver, but not in spleen, is Fc-dependent; that complement enhances IgM-mediated GXM sequestration in liver but not spleen; and that CD4 T cells are not necessary for serum GXM clearance. The results have important implications for the eventual use of MAbs in treatment of cryptococcosis.
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U2 - 10.1086/515329
DO - 10.1086/515329
M3 - Article
C2 - 9607845
AN - SCOPUS:0031748919
SN - 0022-1899
VL - 177
SP - 1647
EP - 1659
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -