Nitric oxide (NO) is a cellular mediator and regulator of multiple biologic functions. NO released by alveolar macrophages (AM) is suggested to play a role in mediating pulmonary injury. In murine and rat macrophages, the expression of inducible NO synthase (iNOS) and the release of NO are well established. However, the existence of such a pathway in other species remains controversial. In this study, we examined NO production and iNOS expression by AM from rats and hamsters, two laboratory animal species that are characterized by their disparate pulmonary responses to various inhaled irritants/toxicants. AM were treated with lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), or tumor necrosis factor-alpha (TNF-alpha) in vitro, and nitrite, the stable oxidation product of NO, was assayed by the Griess reaction. Rat AM produced NO in a dose- and time-dependent manner upon stimulation with LPS and/or IFN-gamma, but not with TNF-alpha. Surprisingly, hamster AM did not release detectable levels of NO after the same treatment. Although iNOS expression was demonstrated in rat AM by immunocytochemical and Western blot analyses, no induction of iNOS expression could be found in hamster AM. Using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, we found that rat and hamster AM could be induced to express iNOS mRNA after treatment with LPS and IFN-gamma. The results presented here indicate that hamster AM, in contrast to rat AM, lack the ability to express iNOS protein and to generate NO in response to LPS, IFN-gamma, or TNF-alpha in vitro. In conclusion, our data suggest striking differences in iNOS regulation and NO production by AM from rats and hamsters, two rodent species that are commonly used in biomedical research and well-known for their disparate responses to pulmonary irritants/toxicants.

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Several epidemiological studies have described an association between adverse health effects and exposure to mould and microbes present in the indoor air of moisture-damaged buildings. However, the biochemical linkage between microbial exposure and the large variety of reported respiratory symptoms is poorly understood.In the present study, the authors compared the respiratory symptoms, the production of inflammatory mediators interleukin (IL)-1, IL-4, IL-6, tumour necrosis factor-a (TNF-a) and cell count in nasal lavage fluid and induced sputum samples of subjects working in moisture-damaged and control school buildings. The sampling was performed and the questionnaires were completed at the end of the spring term, at the end of the summer vacation (2.5 months), during the winter term and after a 1-week winter holiday.The authors found a significant elevation of IL-1, TNF-a and IL-6 in nasal lavage fluid and IL-6 in induced sputum during the spring term in the subjects from the moisture-damaged school building compared to the subjects from the control building. The exposed workers reported sore throat, phlegm, eye irritation, rhinitis, nasal obstruction and cough in parallel with these findings.The present data suggests an association between microbial exposure, and symptoms as well as changes in pro-inflammatory mediators detected from both the upper and lower airways. Eur Respir J 2001; 18: 951-958.

We investigated the seasonal variations in the chemical composition and in vivo inflammatory activity of urban air particulate samples in four size ranges (PM(10-2.5), PM(2.5-1), PM(1-0.2), and PM(0.2)). The samples were collected in Helsinki using a high-volume cascade impactor (HVCI). Healthy C57BL/6J mice were intratracheally instilled with a single dose (10 mg/kg) of the particulate samples. The lungs were lavaged and the bronchoalveolar lavage fluid (BALF) was assayed for indicators of inflammation and tissue damage: cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, and keratinocyte-derived chemokine [KC]) at 4 h, and total cell number and total protein concentration at 12 h. The PM(10-2.5) and PM(2.5-1) samples had much higher inflammatory potency than the PM(1-0.2) and PM(0.2) samples. The relative inflammatory activities of the autumn samples were the highest on an equal mass basis, but when estimated for the particulate mass per cubic meter of air, the springtime samples had the highest inflammatory potential. Resuspended soil material and other non-exhaust particulate material from traffic were associated with a high inflammatory activity of the PM(10-2.5) and PM(2.5-1) samples. Secondary inorganic ions in the PM(1-0.2) and PM(0.2) samples had inconsistent negative or positive correlations with the inflammatory activity. There were no systematic seasonal variations in the tracers of incomplete combustion and atmospherically oxidized organics in the PM(1-0.2) and PM(0.2) samples, which probably explains their low correlations with the inflammatory activity. In conclusion, in a relatively clean Nordic city, the resuspension of road dust and other non-exhaust particulate material from traffic were the major sources of inflammatory activity of urban air inhalable particles.

There is abundant documentation of the association between building dampness and mold and adverse health effects on occupants, but the causal agents of the effects are still unclear. In order to reveal these causal links, experimental studies with in vitro and in vivo methods are needed. The present findings shed new light on studies of the microbial constituents of indoor air in moldy buildings responsible for adverse health effects. These results imply that bacteria should also be monitored in cases of suspected microbial contamination of indoor air.