M. Grinsell et al., In vivo clearance of glucuronoxylomannan, the major capsular polysaccharide of Cryptococcus neoformans: A critical role for tissue macrophages, J INFEC DIS, 184(4), 2001, pp. 479-487
Cryptococcus neoformans produces a life-threatening meningitis in patients
who are immunocompromised by AIDS. A striking feature of cryptococcosis in
AIDS is high serum levels of the major capsular polysaccharide, glucuronoxy
lomannan (GXM). Soluble GXM has numerous biologic activities that may contr
ibute to the pathogenesis of infection. The objective of the study was to f
urther understand in vivo processing of GXM. Mice were injected intravenous
ly with GXM, and the tissue distribution was determined. A macrophage suici
de technique that used liposome-encapsulated dichloromethylene diphosphonat
e determined the role of macrophages. GXM was cleared from serum with a hal
f-life of 24-48 h but was retained for an indefinite period in tissues rich
in cells of the mononuclear phagocyte system. Ablation of macrophages decr
eased GXM in the liver and spleen and increased serum GXM. The results iden
tify a key role for macrophages in the clearance of GXM from serum and iden
tify macrophages as a long-term reservoir for storage.