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. 1981 Sep 1;90(3):656–664. doi: 10.1083/jcb.90.3.656

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

PMCID: PMC2111913  PMID: 7287819

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.

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Selected References

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  1. BAER J. E., BEYER K. H., PAULSON S. F., RUSSO H. F. Renal elimination of 3-methylaminoisocamphane hydrochloride (mecamylamine). Am J Physiol. 1956 Jul;186(1):180–186. doi: 10.1152/ajplegacy.1956.186.1.180. [DOI] [PubMed] [Google Scholar]
  2. BELKIN M., HARDY W. G., ORR H. C., LACHMAN A. B. Induction in vitro by autonomic drugs of cytoplasmic vacuoles in ascites tumor cells. J Natl Cancer Inst. 1962 Jan;28:187–201. [PubMed] [Google Scholar]
  3. Bulychev A., Trouet A., Tulkens P. Uptake and intracellular distribution of neutral red in cultured fibroblasts. Exp Cell Res. 1978 Sep;115(2):343–355. doi: 10.1016/0014-4827(78)90288-4. [DOI] [PubMed] [Google Scholar]
  4. COHN Z. A., BENSON B. THE DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES. MORPHOLOGY, CYTOCHEMISTRY, AND BIOCHEMISTRY. J Exp Med. 1965 Jan 1;121:153–170. doi: 10.1084/jem.121.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Edelson P. J., Cohn Z. A. Effects of concanavalin A on mouse peritoneal macrophages. I. Stimulation of endocytic activity and inhibition of phago-lysosome formation. J Exp Med. 1974 Nov 1;140(5):1364–1386. doi: 10.1084/jem.140.5.1364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Finnin B. C., Reed B. L., Ruffin N. E. The effects of osmotic pressure on procaine-induced vacuolation in cell culture. J Pharm Pharmacol. 1969 Feb;21(2):114–117. doi: 10.1111/j.2042-7158.1969.tb08207.x. [DOI] [PubMed] [Google Scholar]
  7. Goldman R., Raz A. Concanavalin A and the in vitro induction in macrophages of vacuolation and lysosomal enzyme synthesis. Exp Cell Res. 1975 Dec;96(2):393–405. doi: 10.1016/0014-4827(75)90273-6. [DOI] [PubMed] [Google Scholar]
  8. Leighton F., Poole B., Beaufay H., Baudhuin P., Coffey J. W., Fowler S., De Duve C. The large-scale separation of peroxisomes, mitochondria, and lysosomes from the livers of rats injected with triton WR-1339. Improved isolation procedures, automated analysis, biochemical and morphological properties of fractions. J Cell Biol. 1968 May;37(2):482–513. doi: 10.1083/jcb.37.2.482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Morton H. J. A survey of commercially available tissue culture media. In Vitro. 1970 Sep-Oct;6(2):89–108. doi: 10.1007/BF02616112. [DOI] [PubMed] [Google Scholar]
  10. Ohkuma S., Poole B. Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3327–3331. doi: 10.1073/pnas.75.7.3327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Poole B., Ohkuma S. Effect of weak bases on the intralysosomal pH in mouse peritoneal macrophages. J Cell Biol. 1981 Sep;90(3):665–669. doi: 10.1083/jcb.90.3.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Reijngoud D. J., Tager J. M. The permeability properties of the lysosomal membrane. Biochim Biophys Acta. 1977 Nov 14;472(3-4):419–449. doi: 10.1016/0304-4157(77)90005-3. [DOI] [PubMed] [Google Scholar]
  13. Seglen P. O., Reith A. Ammonia inhibition of protein degradation in isolated rat hepatocytes. Quantitative ultrastructural alterations in the lysosomal system. Exp Cell Res. 1976 Jul;100(2):276–280. doi: 10.1016/0014-4827(76)90148-8. [DOI] [PubMed] [Google Scholar]
  14. Setnikar I. Ionization of bases with limited solubility. Investigation of substances with local anesthetic activity. J Pharm Sci. 1966 Nov;55(11):1190–1195. doi: 10.1002/jps.2600551104. [DOI] [PubMed] [Google Scholar]
  15. Wibo M., Poole B. Protein degradation in cultured cells. II. The uptake of chloroquine by rat fibroblasts and the inhibition of cellular protein degradation and cathepsin B1. J Cell Biol. 1974 Nov;63(2 Pt 1):430–440. doi: 10.1083/jcb.63.2.430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. YANG W. C., STRASSER F. F., POMERAT C. M. MECHANISM OF DRUG-INDUCED VACUOLIZATION IN TISSUE CULTURE. Exp Cell Res. 1965 Jun;38:495–506. doi: 10.1016/0014-4827(65)90373-3. [DOI] [PubMed] [Google Scholar]
  17. de Duve C., de Barsy T., Poole B., Trouet A., Tulkens P., Van Hoof F. Commentary. Lysosomotropic agents. Biochem Pharmacol. 1974 Sep 15;23(18):2495–2531. doi: 10.1016/0006-2952(74)90174-9. [DOI] [PubMed] [Google Scholar]

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