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Rat alveolar macrophages incubated with recombinant rat interferon-gamma produce L-arginine-dependent nitric oxide, which is rapidly decomposed into nitrite: this production by interferon-gamma was markedly enhanced by granulocyte-macrophage colony-stimulating factor and muramyldipeptide, but not by other cytokines. The enhancement was dependent on the presence of L-arginine in the incubation medium. It was based on a simple synergism between interferon-gamma and muramyldipeptide and a priming effect of granulocyte-macrophage colony-stimulating factor for interferon-gamma-induced nitrite production. These data suggest that cytokine networks are important in the induction of nitric oxide in rat alveolar macrophages.

Mast cells from infant foreskin obtained during circumcision were dispersed by an enzymatic technique, pooled, washed and purified. Mast cells, with a purity of 70–90% were incubated with 10−11 to 10−7M rTNFα. Histamine and tryptase levels were assessed in the cell supernatant and a concentration dependent release of histamine was observed. Histamine reached a maximum of 11.5±2.2 nmol/106 cells at 10−8M rTNF. Tryptase reached a maximum of 293±105 mU/106 cells (10−8M rTNF). rTNFα thus appears to be a direct stimulus for mast cells to degranulate and to release both histamine and tryptase.

We have investigated the effects of the nitric oxide donor sodium nitroprusside on the immunologic release of histamine and tryptase from human mast cells. Isolated human skin mast cells were purified using Percoll gradient centrifugation. Mast cells with a purity of 70–90% were preincubated for 30 minutes with sodium nitroprusside and subsequently stimulated with anti-IgE. Upon challenge with anti-IgE, a release of 6.37±0.46 nmol histamine and 612±49 ng tryptase per 106 cells was observed. In presence of sodium nitroprusside a dose-dependent decrease of the release occurred. The results suggest that nitric oxide is effective in reducing the release of histamine and tryptase from human skin mast cells.