The proposed research is aimed at characterizing and investigating the cellular physiology of the human peripheral blood lymphocyte in order to determine the role of various regulatory mechanisms in cell activation. We shall investigate the molecular basis for regulation of intracellular pH, determine the effect of mitogens on this regulation, and examine the ability of mitogen-stimulated lymphocytes, at various stages of activation, to volume regulate in response to hypotonicity. In addition, ionic modulation of cell contents, cell membrane, cell volume, T-cell receptor expression and growth factor production, and stimulated proliferation will be evaluated in both normal and mitogen-treated lymphocytes. These studies will thus provide a greater understanding of the fundamental molecular mechanisms of lymphocyte homeostasis and blastogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM027595-06
Application #
3151765
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1980-09-01
Project End
1988-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Deutsch, C (1990) K+ channels and mitogenesis. Prog Clin Biol Res 334:251-71
Lee, S C; Price, M; Prystowsky, M B et al. (1988) Volume response of quiescent and interleukin 2-stimulated T-lymphocytes to hypotonicity. Am J Physiol 254:C286-96
Deutsch, C; Lee, S C (1988) Cell volume regulation in lymphocytes. Ren Physiol Biochem 11:260-76
Deutsch, C; Krause, D; Lee, S C (1986) Voltage-gated potassium conductance in human T lymphocytes stimulated with phorbol ester. J Physiol 372:405-23
Lee, S C; Sabath, D E; Deutsch, C et al. (1986) Increased voltage-gated potassium conductance during interleukin 2-stimulated proliferation of a mouse helper T lymphocyte clone. J Cell Biol 102:1200-8
Sabath, D E; Monos, D S; Lee, S C et al. (1986) Cloned T-cell proliferation and synthesis of specific proteins are inhibited by quinine. Proc Natl Acad Sci U S A 83:4739-43
Erecinska, M; Deutsch, C J (1985) Osmotic effects on bacterial transport and energetics. FEBS Lett 188:145-9