Nitric oxide (NO) down regulates the neutrophil CD18 receptor and is purported to decrease lung inflammation. However, in clinical situations, NO is used in the presence of oxygen (O2), a lung inflammatory gas.

Thirty piglets, 10-14 d old, were exposed in chambers to room air (RA), RA+ NO, O2, or O2 + NO for 4-5 d and sacrificed. Ten additional animals received RA + NO, or RA + O2 for 3 d, then recovered 3 d. At sacrifice, 10 ml of right atrial blood was collected into heparinized tubes for neutrophil baseline and PMA-stimulated surface CD18 (DAKO clone MHM23) expression by flow cytometry. Lung sections fixed in 4% formalin were immunohistochemically stained using a polyclonal myeloperoxidase (MPO) antibody (DAKO) and scored on a 1-3 scale. MPO activity was also measured biochemically in lung homogenates, by spectrophotometer, and was expressed as units of MPO/lung/min.

Baseline neutrophil CD18 was similar in all groups. Stimulated neutrophil CD18 in NO + RA pigs was only 57% of RA values (p<0.0002). Oxygen, with or without NO, significantly increased stimulated neutrophil CD18 by 50%(p<0.05). MPO in immunohistochemically stained lung tissue was significantly elevated in O2 and O2 + NO groups. In lung homogenates, RA was not different from RA + NO, but MPO activity was significantly increased with O2 and O2 + NO. The 3-d recovery returned MPO to normal. We conclude that stimulated CD18 neutrophil receptors are significantly decreased by NO in RA-breathing pigs; however, lung neutrophil MPO values do not change. Oxygen overrides the effect of NO, with both up regulation of the receptor and increased MPO in the lungs. The biologic effects of NO inhibiting neutrophil responsiveness and inflammation are nullified by the effects of inhaled O2.