Inhibition of granulocytic-macrophagic precursor cells (CFU-C) by heat-labile enterotoxin (LT) produced by Escherichia coli.
Enterotoxigenic strains of Escherichia coli cause diarrhea by production of heat-labile enterotoxin (LT) which acts through stimulation of membrane-bound adenylate-cyclase in epithelial cells. We studied in vitro production of LT by growing E. coli H 10407 in different synthetic media in comparison with Penassay broth. Non-toxigenic E. coli K12 was used as control. We obtained positive response in Y-1 cell assay for LT activity with all filtrates from E. coli H 10407 cultures. These filtrates inhibit 3H-thymidine uptake by Ehrlich Ascites Carcinoma (EAC) cells and the proliferation of granulocytic-macrophagic precursors (CFU-C) in murine bone marrow. Filtrates did not stimulate CFU-C in absence of CSF. Heat-treated (121 degrees C for 30 minutes) and dialyzed (molecular cut 15,000 daltons) filtrates lost their cytotoxicity against Y-1 cells maintaining the inhibitory activity on CFU-C proliferation. This phenomenon may be regarded as the result of a competitive mechanism between LT and CSF (Colony Stimulating Factor) on the receptor system of committed stem cells.
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000032:analysis; D004768:Enterotoxins / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins; D005260:Female; D006098:Granulocytes / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D013936:Thymidine / Q000378:metabolism
D001427:Bacterial Toxins; D003115:Colony-Stimulating Factors; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C027538:heat-labile enterotoxin, E coli; D013936:Thymidine