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Relationships between pulmonary inflammation, plasma transudation, and oxygen metabolite secretion by alveolar
Abstract:
We have previously shown that alveolar macrophages from normal rabbit lungs do not synthesize reactive oxygen intermediates unless first conditioned by culture in vitro in the presence of serum for 24 to 48 hr. This conditioning process is mediated by a serum constituent that partitions on gel exclusion columns with an apparent m.w. of 30,000 to 50,000 daltons. Alveolar macrophage conditioning in vitro requires protein synthesis, is associated with the generation of membrane NADPH oxidase activity, and is reversible. We have predicted therefore that during the course of pulmonary inflammation, as observed 3 wk after i.v. injection of M. butyricum in oil, alveolar macrophages might similarly become conditioned in vivo through exposure to plasma protein transudates reaching the alveolus. In support of this hypothesis we show that after experimental production of granulomatous pulmonary inflammation in rabbits, alveolar macrophages showed an augmented capacity to secrete superoxide anion when stimulated with phorbol ester, and this enhancement increases exponentially with increased plasma transudation. This augmented enhancement was reversible, and decreased after culture in vitro in the absence of serum. Mature alveolar macrophages were responsible for this enhanced superoxide anion production rather than freshly emigrated monocytes. Moreover, superoxide anion production in this model of pulmonary inflammation appears to be an "all-or-none" phenomenon, with superoxide anion production associated with a subpopulation of optimally conditioned alveolar macrophages, whereas the remaining unconditioned alveolar macrophages produce little or none. We feel that these two classes of alveolar macrophages may be derived from inflamed and noninflamed regions of the lung, respectively, thereby reflecting the discontinuous nature of the inflammatory lesions themselves. Thus we propose that measurements of reactive oxygen intermediate production by lavaged alveolar macrophages may provide a semi-quantitative measure of chronic pulmonary inflammation.
Insights
Pulmonary inflammation conditions alveolar macrophages in vivo, increasing their reactive oxygen intermediate production. This suggests measuring these intermediates can assess chronic lung inflammation.
Area of Science:
- Immunology
- Pulmonary Medicine
- Cell Biology
Background:
- Alveolar macrophages normally require in vitro conditioning with serum to produce reactive oxygen intermediates.
- This conditioning involves a serum factor and requires protein synthesis, NADPH oxidase activity, and is reversible.
Purpose of the Study:
- To investigate if alveolar macrophages become conditioned in vivo during pulmonary inflammation.
- To determine if this in vivo conditioning enhances reactive oxygen intermediate production.
Main Methods:
- Experimental granulomatous pulmonary inflammation was induced in rabbits.
- Alveolar macrophages were lavaged and stimulated with phorbol ester to measure superoxide anion secretion.
- Plasma transudation levels were quantified.
Main Results:
- Alveolar macrophages from inflamed lungs showed enhanced superoxide anion secretion, correlating with plasma transudation.
- This enhancement was reversible and primarily attributed to mature alveolar macrophages, not monocytes.
- Superoxide anion production was an "all-or-none" phenomenon in subpopulations of macrophages.
Conclusions:
- In vivo conditioning of alveolar macrophages occurs during pulmonary inflammation, increasing their reactive oxygen intermediate production.
- This phenomenon is linked to plasma protein exposure in the alveoli.
- Measuring reactive oxygen intermediate production by lavaged alveolar macrophages may serve as a semi-quantitative indicator of chronic pulmonary inflammation.