HYPOXEMIA REOXYGENATION DOWN-REGULATES INTERLEUKIN-8-STIMULATED BACTERICIDAL ACTIVITY OF POLYMORPHONUCLEAR NEUTROPHIL BY DIFFERENTIAL REGULATION OF CD16 AND CD35 MESSENGER-RNA EXPRESSION/

Background, The purpose Of this study was to determine the effects of hypoxemia/reoxygenation (H/R) on the regulation of interleukin-8 (IL-8 )-stimulated human polymorphonuclear neutrophil (PMN) bactericidal act ivity. Methods, Venous human whole blood was rendered normoxic (PvO(2) saturation 60% to 80%), hypoxemic (PvO(2) saturation, less than 15%), or H/R (PvO(2) saturation more than 97%) by dialyzing the blood again st a gas mixture of N-2/H-2/CO2 +/- 30% O-2. Two hundred microliter al iquots from each study group were incubated with IL-8 (50 ng/ml) for 4 5 minutes before fluorescein isothiocyanate-conjugated mouse antihuman CD16 or CD35 antibodies were added. Bactericidal activity was measure d with the release of Cr-51 from labeled bacteria at 1:1, 5:2, and 10: 1 PMN-target ratios. Steady-state mRNA levels for CD16 and CD35 were q uantified by Northern blot analyses. Results, H/R reduced PMN bacteric idal activity compared with hypoxemic levels for staphylococcus aureus (48 +/- 5.6 versus 27 +/- 3.3) and Escherichia coli (58 +/- 7.1 verse s 33 +/- 4.2). H/R reduced the surface expression of CD16 but not CD35 (mean channel fluorescence CD16, 610 +/- 70 versus 310 +/- 30 for hyp oxemia versus H/R; p < 0.01). After H/R was performed, IL-8 decreased mRNA levels for CD16 but not for CD35 compared with levels seen during hypoxemia + IL-8. Conclusions, H/R down-regulates IL-8-stimulated PMN bactericidal activity by decreasing steady-state mRNA levels and surf ace expression of CD16. PMN bactericidal capability after H/R + IL-8 i s primarily complementary and not Fc gamma receptor dependent.