Impairment of lymphocyte adhesion to cultured fibroblasts and endothelial cells by [gamma]-irradiation
- Univ. of Connecticut School of Medicine, Newington, CT (United States)
- Institute of Arthritis and Autoimmunity, West Haven, CT (United States)
A critical component of immune responsiveness is the localization of effector cells at sites of inflammatory lesions. Adhesive molecules that may play a role in this process have been described on the surfaces of both lymphocytes and connective tissue cells. Adhesive interactions of T lymphocytes with fibroblasts or endothelial cells can be inhibited by preincubation of the fibroblasts or endothelial cells with antibody to intercellular adhesion molecule 1 (CD54) or by preincubation of the T cells with antibody to lymphocyte function-associated Ag 1 (CD11a/CD18), molecules shown to be important in several other cell-cell adhesion interactions. Here the authors show that [gamma]-irradiation of human T lymphocytes impaired their ability to adhere to both fibroblasts and endothelial cells. This impairment was not associated with a loss of cell viability or of cell surface lymphocyte function-associated Ag 1 expression. [gamma]-Irradiation of T cells is known to result in the activation of ADP-ribosyltransferase, an enzyme involved in DNA strand-break repair, causing subsequent depletion of cellular nicotinamide adenine dinucleotide (NAD) pools by increasing NAD consumption for poly(ADP-ribose) formation. Preincubation of T cells with either nicotinamide or 3-aminobenzamide, both known inhibitors of ADP-ribosyltransferase, completely reversed the suppressive effects of [gamma]-irradiation on T cell adhesion. The maintenance of adhesion was accompanied by inhibition of irradiation-induced depletion of cellular NAD. These experiments suggest that the impairment of cellular immune function after irradiation in vivo may be caused, in part, by defective T cell emigration and localization at inflammatory sites. 44 refs., 5 figs., 3 tabs.
- OSTI ID:
- 7199235
- Journal Information:
- Journal of Immunology; (United States), Vol. 148:1; ISSN 0022-1767
- Country of Publication:
- United States
- Language:
- English
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ENDOTHELIUM
ADHESION
BIOLOGICAL RADIATION EFFECTS
FIBROBLASTS
LYMPHOCYTES
DNA REPAIR
GAMMA RADIATION
STRAND BREAKS
ANIMAL CELLS
ANIMAL TISSUES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CONNECTIVE TISSUE CELLS
ELECTROMAGNETIC RADIATION
IONIZING RADIATIONS
LEUKOCYTES
MATERIALS
RADIATION EFFECTS
RADIATIONS
REPAIR
SOMATIC CELLS
TISSUES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture