DNA activates human polymorphonuclear leukocytes--a new importance of DNA presented in the inflammatory...

DNA from calf thymus (1 to 10 micrograms/ml) was shown to stimulate the release of myeloperoxidase (MPO) and low amounts of H2O2 (about 1.5 nmoles/10(6) cells) from human polymorphonuclear leukocytes (PMNL). PMNL during 60 min incubation with DNA (10 micrograms/ml) and with DNA and cytochalasin B (4.8 micrograms/ml) released 14.4 +/- 3.4 and 25.5 +/- 4.8% (n = 7) of the total MPO cell activity, respectively. Higher DNA concentrations (0.25 to 1mg/ml) were chemotactic for PMNL as assayed under agarose method. At DNA concentration 1mg/ml the chemotactic index reached 1.5 +/- 0.2 and was approximate to value 1.7 +/- 0.2 (n = 7) obtained with zymosan-activated serum. However, the introduction of DNA to the mouse pleural cavity caused insignificant increase in the number of PMNL and lymphocytes recovered from the cavity at 3 h after injection, comparing it to material obtained from buffer-treated animals. The yield of DNA preparation from purulent sputum (about 10 micrograms/ml) indicates that DNA concentrations which activate PMNL in vitro occur in the inflammatory tracheobronchial secretion. The DNA from sputum electrophoresed on the 0.6% agarose gel reveal pattern which could be the result of nucleosomal DNA degradation. These results suggest that DNA released from nuclear debris in the place of inflammation, especially in the lower respiratory tract could secondarily modulate its course by PMNL activation. This novel role of DNA may be important for pulmonary pathology since lungs are susceptible to proteolytic and oxidant mediated injury.