NO Production by Human M and Glia

Because of the ease with which one can induce abundant NO production in rodent M4 cultures, scientists have been perplexed at the contradictory and somewhat controversial findings in vitro with human peripheral blood M ) cultures (Denis, 1994). While some reports have failed to see NO synthesis as measured by nitrite (NO2) or by consumption of arginine in M h stimulated with bacterial products or lymphokines or even after infection with fungal or microbial agents (reviewed by Denis, 1994 Schneemann et al., 1993), several other studies have demonstrated that M4 cultured for a minimum period of 72 hr with or without stimuli produced nanomolar to micromolar NO2 (Denis, 1991 Munoz-Fernandez et al., 1992 Martin and Edwards, 1993). Of interest is the fact that one of the negative studies examined NO2 after only 48 hr (Schneeman et al., 1993). It seems that maximal NO activity in human M ) may require stimulation for 5-7 days in vitro (Denis, 1991 Martin and Edwards, 1993), in contrast to the rodent M ), which produce NO within 24 hr after stimulation. 

and granulocyte-Mc]) colony-stimulating factor induce NO-mediated protection against intracellular pathogens. Combinations of cytokines are more potent at induction than individual cytokines or lipopoly-saccharide (EPS), which is a poor inducer (Denis, 1991 Munoz-Fernandez, 

it is important to note this is another difference between humans and rodents, in which IFN-y or LPS alone can induce NO in M . 

Pietraforte et al. (1994) have recently examined the effect of gpl20 envelope protein from HIV-1 on NO induction in human M f , using electron paramagnetic resonance spin trapping and NOl production. They detected a two- to threefold increase in NOi over control values within 15 hr. Dexamethasone sensitivity suggested that this was iNOS mediated. Interestingly, it was not CD4 mediated, suggesting an interaction of virus with immune cells unique from that described for infection (Pietraforte et al., 1994). 

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