Pulmonary intravascular macrophages (PIMs) are present in ruminants and horses. These species are highly sensitive to acute lung inflammation compared with non-PIM-containing species such as rats and humans. There is evidence that rats and humans may also recruit PIMs under certain conditions. We investigated precise contributions of PIMs to acute lung inflammation in a calf model. First, PIMs were recognized with a combination of in vivo phagocytic tracer Monastral blue and postembedding immunohistology with anti-CD68 monoclonal antibody. Second, gadolinium chloride depleted PIMs within 48 h of treatment (P < 0.05). Finally, PIMs contain TNF-alpha, and their depletion reduces cells positive for IL-8 (P < 0.05) and TNF-alpha (P < 0.05) and histopathological signs of acute lung inflammation in calves infected with Mannheimia hemolytica. The majority of IL-8-positive inflammatory cells in lung septa of infected calves were platelets. Platelets from normal cattle contained preformed IL-8 that was released upon in vitro exposure to thrombin (P < 0.05). These novel data show that PIMs, as the source of TNF-alpha, promote recruitment of inflammatory cells including IL-8-containing platelets to stimulate acute inflammation and pathology in lungs. These data may also be relevant to humans due to our ability to recruit PIMs.
BackgroundExposure to swine barn air is an occupational hazard. Barn workers following an eight-hour work shift develop many signs of lung dysfunction including lung inflammation. However, the in situ cellular and molecular mechanisms responsible for lung dysfunction induced following exposure to the barn air remain largely unknown. Specifically, the recruitment and role of pulmonary intravascular monocytes/macrophages (PIMMs), which increase host susceptibility for acute lung inflammation, remain unknown in barn air induced lung inflammation. We hypothesized that barn exposure induces recruitment of PIMMs and increases susceptibility for acute lung inflammation with a secondary challenge.MethodsSprague-Dawley rats were exposed either to the barn or ambient air for eight hours and were euthanized at various time intervals to collect blood, broncho-alveolar lavage fluid (BALF) and lung tissue. Subsequently, following an eight hour barn or ambient air exposure, rats were challenged either with Escherichia coli (E. coli) lipopolysaccharide (LPS) or saline and euthanized 6 hours post-LPS or saline treatment. We used ANOVA (P < 0.05 means significant) to compare group differences.ResultsAn eight-hour exposure to barn air induced acute lung inflammation with recruitment of granulocytes and PIMMs. Granulocyte and PIMM numbers peaked at one and 48 hour post-exposure, respectively.Secondary challenge with E. coli LPS at 48 hour following barn exposure resulted in intense lung inflammation, greater numbers of granulocytes, increased number of cells positive for TNF-α and decreased amounts of TGF-β2 in lung tissues. We also localized TNF-α, IL-1β and TGF-β2 in PIMMs.ConclusionA single exposure to barn air induces lung inflammation with recruitment of PIMMs and granulocytes. Recruited PIMMs may be linked to more robust lung inflammation in barn-exposed rats exposed to LPS. These data may have implications of workers exposed to the barn air who may encounter secondary microbial challenge.
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