Expression of Ia-antigens on normal and chronic myeloid leukemic human granulocyte-macrophage colony-forming cells (CFU-GM) is associated with the regulation of cell proliferation by prostaglandin E.
The presence of la-antigens and their relationship to the inhibitory effect of prostaglandin E on the proliferation of human CFU-GM was studied in animals and patients with chronic myeloid leukemia. Consistent reduction of normal colony formation to approximately 50% of baseline levels was observed using a monoclonal anti-human la antibody in a complement-dependent cytotoxicity assay titrated over serial dilutions. ELimination of the la-antigen-bearing CFU-GM population was associated with virtually a complete loss of responsiveness to the inhibitory effects of prostaglandin E. Maintenance of bone marrow cells in short-term suspension culture at 37 degrees C prior to agar culture resulted in the loss of detectable la-antigen on the CFU-GM and, similarly, loss of response to prostaglandin. In contrast, most patients with chronic myeloid leukemia showed greatly reduced levels of la-antigens on their CFU-GM in fresh marrow together with lack of prostaglandin sensitivity, suggesting a correlation with the abnormal growth regulation observed in these patients. In two chronic myeloid leukemia patients, levels of la-antigen higher than that observed in the majority of patients could be detected and correlated with a residual response to prostaglandin E. These results suggest a relationship in normals between the expression of la-antigens on CFU-GM and the physiologic response to regulation by prostaglandin E, and a possible mechanism for the aberrant regulatory response in patients with chronic myeloid leukemia.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D000939:Epitopes; D005260:Female; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D066298:In Vitro Techniques; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011458:Prostaglandins E / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D011458:Prostaglandins E