Original ContributionOxidative stress induces protein and DNA radical formation in follicular dendritic cells of the germinal center and modulates its cell death patterns in late sepsis
Section snippets
Materials
Lipopolysaccharide (LPS; Escherichia coli; strain 55:B5), the iron chelator desferrioxamine mesylate (desferrioxamine), apocynin, the catalase inhibitor aminotriazole (AT), the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT), and allopurinol were obtained from Sigma Chemical Co. (St. Louis, MO, USA). The spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) was obtained from Alexis Biochemicals (San Diego, CA, USA). All other chemicals were of analytical grade and were purchased from Sigma
LPS-induced sepsis-like syndrome forms cytosolic and nuclear protein radicals in germinal center FDCs and HK cells
Sepsis-like syndrome and other acute inflammatory insults result in copious generation of ROS, primarily in the form of superoxide radicals and nonradicals such as H2O2 and peroxynitrite [14], [25], [26], [27], [28]. Though the initial generation of ROS contributes to the hyperinflammatory state, the resultant cellular stress may alter cell signaling, leading to cell death [29]. FDCs, by functioning as accessory cells in the immune system, play a major role in germinal center reactions of the
Discussion
Mortality and morbidity in sepsis are now known to be the results of severe immunosuppression, termed immunoparalysis. This condition is caused primarily by the profound depletion of lymphocytes, dendritic cells, interdigitating cells, and follicular dendritic cells; enhanced dendritic cell survival attenuates LPS-induced immunosuppression [2], [3], [36], [37], [38]. The rapid depletion of the immune effector cells is primarily due to apoptotic-like processes, and the molecular mechanisms
Acknowledgments
The authors sincerely acknowledge Tiwanda Marsh, Jeoffrey Hurlburt, and Holly Rutledge for excellent technical assistance. We also thank Dr. Carl Bortner for help in analyzing flow cytometry data and Dr. Shyamal Peddada of the Statistics Branch, NIEHS, for generous help in statistical analysis. We also sincerely thank Dr. Ann Motten and Mary Mason for help in the careful editing of the manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health
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