Malakoplakia: evidence for monocyte lysosomal abnormality correctable by cholinergic agonist in vitro and in vivo.

Abstract

We studied monocyte function in a case of malakoplakia in an attempt to characterize the immune defect in this condition. Our patient's intracellular cyclic-GMP levels were abnormally low (mean +/- S.D. of 0.17 +/- 0.05 pmol per 10(7) malakoplakia cells, versus 0.79 +/- 0.12 in normals) p less than 0.001). After phagocytosis, his monocytes failed to release beta-glucuronidase. In the bactericidal assay, incubation of the patient's monocytes with Escherichia coli allowed growth of 542 +/- 46 colonies, normal monocytes allowed 95 +/- 22 (p less than 0.001). The percentage of monocytes with large lysosomal granules was 23 +/- 4 in the patient and 4 +/- 2 in normal controls. After in vitro incubation of the patient's cells or in vivo treatment with bethanechol chloride, the cyclic-GMP levels, bactericidal ability and lysosomal granules of the cells returned to normal levels. Low levels of cyclic-GMP could impair lysosomal function and bacterial killing in this condition. Cholinergic agonists correct the in vitro abnormalities and are beneficial in vivo.

• Authors: N I Abdou, C NaPombejara, A Sagawa, C Ragland, D J Stechschulte, U Nilsson, W Gourley, I Watanabe, N J Lindsey, M S Allen
• Journal: The New England journal of medicine (N Engl J Med) Vol. 297 Issue 26 Pg. 1413-9 (Dec 29 1977) ISSN: 0028-4793 [Print] United States
• PMID: 200843 (Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Bethanechol Compounds
• Parasympathomimetics
• Cyclic GMP

Topics

• Adult
• B-Lymphocytes (immunology)
• Bethanechol Compounds (pharmacology, therapeutic use)
• Blood Bactericidal Activity
• Chemotaxis
• Cyclic GMP (metabolism)
• Escherichia coli
• Humans
• Lysosomes (enzymology)
• Malacoplakia (drug therapy, immunology, pathology)
• Male
• Microtubules (physiology)
• Monocytes (physiology, ultrastructure)
• Parasympathomimetics (therapeutic use)
• Phagocytosis
• T-Lymphocytes (immunology)