Chemotherapeutic stress mediated by certain antitumor antibiotics induces an atypical CD69+ surface phenotype in peripheral T-lymphocytes.
Surface antigen CD69 is a Type II integral membrane protein that is generally considered a cell activation marker expressed very early in the normal lymphocyte activation cascade. The conformation of this surface antigen suggests a putative role in transmembrane signal transduction, yet the precise function of this surface antigen has not been clearly elucidated. We had previously reported robust atypical CD69 expression in peripheral T-lymphocytes as concentration-dependent, phenotypic responses to actinomycin D-induced chemotherapeutic stress in the absence of secondary stimulation. Additional antitumor antibiotics were evaluated for inductive potential, and the incidence and respective magnitudes of this chemotherapeutic stress-induced shift in lymphocytic CD69 expression were assessed. Results indicated that atypical CD69 expression is a common response to chemotherapy drug-induced stress. Differences in the respective percentages of CD69 + T-lymphocytes, and the resulting numbers of CD69 surface antigens ultimately expressed by these cells, were documented following in vitro drug exposure. The effective drug concentrations required to mediate detectable shifts in the CD69+ phenotype differed among the selected drugs, as well, suggesting a concentration-dependent induction mechanism putatively related to drug modality. Static CD69 expression responses in CD3+ peripheral T-lymphocytes were also documented, which further suggests that the different intracellular modalities do not mediate proportional T-lymphocyte responses through elevated CD69 expression.
Morgan
C D
CD
Department of Pathology, Scott & White Memorial Hospital and Clinic, Scott, Sherwood, and Brindley Foundation, Texas A&M University System Health Science Center, Temple 76508, USA. cmorgan@swmail.sw.org
Holguin
M H
MH
D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000276:immunology; D001761:Bleomycin / Q000009:adverse effects; D003609:Dactinomycin / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016130:Immunophenotyping; D037181:Lectins, C-Type; D008353:Mannitol / Q000009:adverse effects; D016685:Mitomycin / Q000009:adverse effects; D008942:Mitoxantrone / Q000009:adverse effects; D008926:Plicamycin / Q000009:adverse effects / Q000031:analogs & derivatives*; D013050:Spectrometry, Fluorescence; D013312:Stress, Physiological / Q000139:chemically induced; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D013936:Thymidine / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099192:CD69 Antigens
D000903:Antibiotics, Antineoplastic; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001761:Bleomycin; D003609:Dactinomycin; D037181:Lectins, C-Type; D008353:Mannitol; D016685:Mitomycin; D008942:Mitoxantrone; D008926:Plicamycin; D013936:Thymidine; D000099192:CD69 Antigens; C066851:mithramycin A