Impairment of lymphocyte adhesion to cultured fibroblasts and endothelial cells by gamma-irradiation.
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 adhesive interactions. Here we 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 benzamide [corrected], 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.
Department of Medicine, VA Medical Center, Newington, CT 06111.
T H
TH
Piela-Smith
T
T
Aune
L
L
Aneiro
E
E
Nuveen
J H
JH
Korn
D000255:Adenosine Triphosphate / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D002448:Cell Adhesion / Q000528:radiation effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology*; D005720:Gamma Rays; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*
D001549:Benzamides; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011994:Recombinant Proteins; D009243:NAD; D018799:Intercellular Adhesion Molecule-1; D009536:Niacinamide; C037689:benzamide; D007371:Interferon-gamma; D000255:Adenosine Triphosphate