Project at a Glance

Title: Effects of multiple day exposure to nitrogen dioxide on human cellular immunity: human macrophage responses.

Principal Investigator / Author(s): Kleinman, Michael T

Contractor: UC Irvine

Contract Number: 95-311

Research Program Area: Health & Exposure

Topic Areas: Health Effects of Air Pollution


Fifteen healthy volunteers were recruited, provided informed consent and were characterized with respect to pulmonary function, airway resistance and non-specific airway reactivity. The subjects were exposed to filtered air (FA) or 2.0 ppm nitrogen dioxide (NO2) for four hours per day, alternating 30-minute periods of rest and exercise, for three consecutive days. Bronchoscopy and bronchoalveolar lavage were performed 1 percent an hour after the third day of either FA or NO2 exposure. Macrophages were recovered from the bronchoalveolar lavage fluid and selected macrophage functions were assayed. Assays were performed for superoxide free radical production by the macrophages before and after stimulation with phorbol myristate acetate (PMA) and before and after stimulation with serum incubated yeast particles (opsonized zymosan). This function, known as respiratory burst activity, is an important part of lung defenses against infectious agents. However, excessive free radical production can overwhelm tissue defenses and cause injury. Other assays that were performed (when there were sufficient numbers of macrophages) included phagocytic activity of the macrophages and production of beta glucuronidase (a lysosomal enzyme important in lung defense against pathogens). These latter assays did not show any clear exposure-related effects, however NO2 exposure increased superoxide release by macrophages incubated with either of the two stimulants; the increase was significant (p 10.05) for PMA stimulation but not for zymosan. Analysis of the data also revealed a significant, but hitherto unreported, relationship between baseline (i.e. unstimulated) free radical release of macrophages and specific airway resistance. We found, in fact, that those subjects with relatively high airway resistance had macrophages with suppressed baseline superoxide production. The findings of this study suggest that macrophages may play a role in mediating normal airway resistance. They also demonstrate that NO2 exposure can interfere with mechanisms that control macrophage responses to stimulation, such that they produce greater amounts of toxic free radicals, compared to macrophages from the same individuals after FA exposure.

For questions regarding this research project, including available data and progress status, contact: Research Division staff at (916) 445-0753

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