Effects of the protein kinase C stimulant bryostatin 1 on the proliferation and colony formation of irradiated human T-lymphocytes.
The protein kinase C stimulant bryostatin 1 (Bryo) was used in examining human peripheral blood T-lymphocyte radiosensitivities in proliferation assays. Bryo was similar to PMA in inducing T-cell proliferation by the CD3, CD28 and CD69 pathways. No difference in radiosensitivities was observed in T-cells stimulated by the three independent surface antigen-mediated activation pathways. CD3 was chosen as the second signal for comparing the potencies of the three different first signals Bryo, phorbol 12-myristate, 13-acetate (PMA), and interleukin 2 (IL-2) in stimulating T-cell proliferation and in maintaining this response after radiation. Though there were radioresponse differences among various individuals, the irradiated lymphocytes consistently showed significantly greater proliferation when treated with Bryo or PMA than with IL-2 (p < 0.05- < 0.005). No difference in proliferative responses was observed in T-cells irradiated between 4 h before and 15 h after the addition of stimulants. Colony forming assays showed higher colony survival for irradiated T-cells stimulated with Bryo than with PMA. These results support the important role of protein kinase C in T-cell radiation responses, and suggest a potential role for Bryo in enhancing T-lymphocyte survival during radiation therapy.
Sung
S J
SJ
Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Lin
P S
PS
Schmidt-Ullrich
R
R
Hall
C E
CE
Walters
J A
JA
McCrady
C
C
Grant
S
S
D000276:Adjuvants, Immunologic; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D054713:Bryostatins; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division / Q000528:radiation effects; D004260:DNA Repair; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000528:radiation effects*; D018942:Macrolides; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects; D011836:Radiation Tolerance; D013601:T-Lymphocytes / Q000187:drug effects / Q000528:radiation effects*; D000099192:CD69 Antigens
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D054713:Bryostatins; D018106:CD28 Antigens; D017252:CD3 Complex; D007783:Lactones; D037181:Lectins, C-Type; D018942:Macrolides; D010703:Phorbol Esters; D011493:Protein Kinase C; D000099192:CD69 Antigens; C046785:bryostatin 1