When do human macrophages release nitric oxide? Variable effects of certain in vitro cultural and in vivo resident conditions.

Abstract

Nitric oxide (NO) release from mouse and rat macrophages is implicated in tumor cell cytotoxicity and the killing of intracellular organisms. Evidence, however, suggests that human monocyte-derived macrophages or myeloid leukemic cells differentiated along the monocytic lineage do not consistently release NO. Results presented herein that human monocyte-derived macrophages in response to lipopolysaccharide can release NO, but markedly less than mouse macrophages (1.26 +/- 0.20 vs 42.5 +/- 6.3 microM). Different in vitro and in vivo conditions have variable effects on NO production by human macrophages. Monocytes cultured in plastic wells, but not teflon beakers, for 7 days can release NO (1.22 +/- 0.13 vs 0.14 +/- 0.07 microM). In addition, human resident macrophages derived from patients with certain diseases possess a calcium- and protein kinase C-dependent pathway to produce NO, in contrast to the calcium-independent and phosphatase-dependent NO release in murine macrophages. Above results suggest that the mechanism of producing NO by macrophages in humans is not only different from that in mice, but also depends on certain in vitro and in vivo conditions.