NITRIC-OXIDE SYNTHASE IS NOT A CONSTITUENT OF THE ANTIMICROBIAL ARMATURE OF HUMAN MONONUCLEAR PHAGOCYTES

Nitric oxide synthase (NOS) has received immense interest as an antimi crobial and antitumoral effector system of mononuclear phagocytes from rodents. Because there is increasing doubt that an analogous system e xists in human macrophages, NOS was reexamined in these cells. Under t ightly controlled conditions, with murine macrophages as positive cont rols, human macrophages failed to secrete nitric oxide (<0.1 mumol/10( 6) cells/24 h), even after activation with endotoxin, interferon-gamma , granulocyte-macrophage colony-stimulating factor, tumor necrosis fac tor-alpha, bacteria, or proliferating lymphocytes. The discrepancy bet ween murine and human macrophages depended on neither the anatomic sou rce (blood, peritoneum), the agent used for activation. nor the durati on of activation. NOS activity was paralleled by metabolization Of L-a rginine to L-citrulline. Exogenous tetrahydrobiopterin, an essential c ofactor of NOS not synthesized by human macrophages, did not support N OS activity in human macrophages. Also, no NOS activity was found in c ellular subfractions of human macrophages. It appears that in humans, the inducible high-output NOS is not conserved as an antimicrobial sys tem of macrophages.