Cytoplasmic vacuolation of mouse peritoneal macrophages and the uptake into lysosomes of weakly basic substances.

TLDR

Weakly basic, lipophilic compounds accumulate in lysosomes, and when the neutral‑form concentration rises sufficiently, osmotic swelling induces vacuolation, with thresholds spanning almost three orders of magnitude. Chloroquine is anomalous, as concentrations above ~30 µM lead to less uptake and vacuolation than lower concentrations.

Abstract

With few exceptions, weakly basic compounds that are sufficiently lipophilic in their neutral forms and sufficiently hydrophilic in their protonated forms accumulate in lysosomes. When the concentration within the lysosomes becomes sufficiently high, osmotic swelling occurs. The cells than take on a vacuolated appearance. The concentrations at which different weak bases cause lysosomal vacuolation vary over almost three orders of magnitude. For any particular weak base, it is the concentration of the neutral form that determines the extent of uptake and the degree of vacuolation. Chloroquine is anomalous in that concentrations greater than approximately 30 microM cause less uptake and less vacuolation than do lower concentrations.