Effect of Immune Mechanisms on the Pharmacokinetics and Organ Distribution

Cryptococcus neoformans is an encapsulated opportunistic fungus that can cause chronic infec-tions accompanied by high tissue levels of capsular polysaccharide (CPS). CPS or its major compo-nent, 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. Capsular polysaccharide (CPS) accumulates in host tissues mediated immunity whereby antibody binds to a toxin and either inhibits its activity or prevents it from reaching its targetduring infection with encapsulated pathogens, such as Strepto-coccus pneumoniae [1], Haemophilus in¯uenzae [2], and tissues. Antibody to CPS may play a role analogous to toxin neutralization by binding CPS and preventing its multiple dele-Cryptococcus neoformans [3]. Microbial CPSs are biologically active molecules that can have a variety of deleterious effects terious effects