Malakoplakia: evidence for monocyte lysosomal abnormality correctable by cholinergic agonist in vitro and in vivo.
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.
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D001626:Bethanechol Compounds / Q000494:pharmacology / Q000627:therapeutic use; D001770:Blood Bactericidal Activity; D002633:Chemotaxis; D006152:Cyclic GMP / Q000378:metabolism; D004926:Escherichia coli; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D008287:Malacoplakia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008870:Microtubules / Q000502:physiology; D009000:Monocytes / Q000502:physiology / Q000648:ultrastructure; D010277:Parasympathomimetics / Q000627:therapeutic use*; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000276:immunology
D001626:Bethanechol Compounds; D010277:Parasympathomimetics; D006152:Cyclic GMP