Morphological aspects of the interaction of Bacillus Calmette-Guérin with urothelial bladder cells in vivo and in vitro: relevance for antitumor activity?
Intravesical administration of Bacillus Calmette-Guérin (BCG) has been shown to be effective in the treatment of patients with superficial bladder cancer. For a better understanding of the mechanism of this antitumor activity, scanning and transmission electron microscope (SEM, TEM) studies were carried out to investigate morphological aspects of the interaction of BCG with the bladder wall in vivo and in vitro. Adherence of BCG to the bladder wall in vivo was studied 1 and 24 h after single or multiple (6x) BCG instillations in intact and in electrocauterized guinea pig bladders. Despite extensive search with SEM for its presence, virtually no BCG was found on the intact urothelium, and BCG was only occasionally observed in the coagulation lesions. SEM and TEM studies revealed adherence and phagocytosis of BCG by the T24 human bladder carcinoma cell line in vitro. Time sequence studies on the phagocytosis and fate of BCG showed that T24 cells are capable of progressively degrading the mycobacteria in phagolysosomes. However, BCG did not alter MHC class II antigen expression on T24 cells in vitro. In contrast, 54 urine sediments and bladder washings of 11 bladder cancer patients, taken prior to or after several intravesical BCG instillations, failed to demonstrate urothelial (tumor) cells showing evidence of BCG phagocytosis (682 cells screened by TEM), while BCG was phagocytized avidly by leukocytes. These data suggest that a direct interaction of BCG with urothelial bladder cells in vivo can be called in question.
Teppema
J S
JS
Laboratory for Pathology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
de Boer
E C
EC
Steerenberg
P A
PA
van der Meijden
A P
AP
D000818:Animals; D001500:BCG Vaccine / Q000494:pharmacology*; D001422:Bacterial Adhesion; D005260:Female; D006168:Guinea Pigs; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D010587:Phagocytosis; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D001743:Urinary Bladder / Q000166:cytology* / Q000276:immunology / Q000382:microbiology; D001749:Urinary Bladder Neoplasms / Q000382:microbiology / Q000473:pathology / Q000628:therapy*
D001500:BCG Vaccine; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II