Repeated lipopolysaccharide (LPS) exposure inhibits HIV replication in primary human macrophages.

Repetitive exposure of macrophages to microbial antigen is known to tolerize them to further stimulation and to inhibit proinflammatory cytokine release. Using transgenic (Tg) mice that incorporate the entire HIV-1 genome we have previously shown that toll like receptor (TLR)-2, -4, and -9 ligands induced tolerance as assessed by decreased proinflammatory cytokine secretion and nuclear factor-kappa beta activation. Yet, despite cytokine modulation, HIV-1 p24 production was enhanced in tolerized cells in vitro and in vivo.

Mechanisms for impaired effector function in alveolar macrophages from marijuana and cocaine smokers.

Lung macrophages provide a first line of host defense against inhaled pathogens and their function is impaired in the lungs of inhaled substance abusers. In order to investigate the mechanism for this impairment, alveolar macrophages (AM) were recovered from nonsmokers (NS), regular tobacco smokers (TS), marijuana smokers (MS), or crack cocaine smokers (CS), and evaluated for their production of nitric oxide (NO) and the role of NO as an antimicrobial effector molecule. AM from NS and TS efficiently killed Staphylococcus aureus and their antibacterial activity correlated closely with the production of nitrite and the expression of mRNA encoding for inducible nitric oxide synthase (iNOS).

Impairment of antimicrobial activity and nitric oxide production in alveolar macrophages from smokers of marijuana and cocaine.

Human alveolar macrophages (AMs) were recovered from the lungs of healthy nonsmokers (NS) or smokers of tobacco (TS), marijuana (MS), or crack cocaine (CS) and challenged in vitro with Staphylococcus aureus. AMs from NS and TS exhibited potent antibacterial activity that correlated with the production of nitric oxide (NO) and induction of NO synthase without the requirement for priming with exogenous cytokines. In contrast, AMs from MS and CS exhibited minimal antibacterial activity and failed to produce NO unless primed with additional cytokines.