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Synthesis of alpha 1-protease inhibitor by resident and activated mouse alveolar macrophages
Abstract:
Alpha 1-protease inhibitor (alpha 1Pi), an acute-phase reactant, is the major inhibitor of neutral proteases causing lung tissue injury, such as elastase. While examining the acute-phase reaction to the nematode parasite Nippostrongylus brasiliensis, we noticed that the alveolar macrophage was closely associated with alpha 1Pi when the larvae were present in the lung. Histologic examination revealed marked edema and hemorrhage with numerous alveolar macrophages that stain intensely for intracellular alpha 1Pi. Isolation of these cells by bronchoalveolar lavage showed the macrophage to be activated. Cultured alveolar macrophages from normal and infected animals synthesized and secreted alpha 1Pi, as revealed by [35S]-methionine incorporation, but the amounts were insignificant compared with that synthesized by hepatocytes. There was, however, no apparent difference in alpha 1Pi synthetic activity between normal and activated macrophages. The presence of demonstrable intracellular alpha 1Pi in the parasite-activated alveolar macrophage likely represents endocytosis as host protease- and/or parasite protease-antiprotease complexes. Although alpha 1Pi is synthesized primarily by hepatocytes, synthesis by alveolar macrophages may provide immediate local protection in the microenvironment of the lung during an acute inflammatory response.
Insights
Alveolar macrophages accumulate alpha 1-protease inhibitor (alpha 1Pi) during parasitic lung infections, suggesting a role in local lung defense. This protective mechanism complements hepatocyte synthesis of alpha 1Pi.
Area of Science:
- Immunology
- Pulmonary Medicine
- Parasitology
Background:
- Alpha 1-protease inhibitor (alpha 1Pi) is a key neutral protease inhibitor, crucial for preventing lung tissue damage from proteases like elastase.
- During parasitic infections, such as Nippostrongylus brasiliensis, alveolar macrophages are observed to interact closely with alpha 1Pi within the lung.
Purpose of the Study:
- To investigate the role and source of alpha 1-protease inhibitor (alpha 1Pi) in alveolar macrophages during parasitic lung infections.
- To determine if alveolar macrophages synthesize alpha 1Pi and if this activity is altered by parasitic activation.
Main Methods:
- Histologic examination of lung tissue from infected animals to assess alpha 1Pi localization in alveolar macrophages.
- Bronchoalveolar lavage to isolate and analyze alveolar macrophages.
- [35S]-methionine incorporation assays to measure alpha 1Pi synthesis in cultured macrophages from normal and infected animals.
Main Results:
- Alveolar macrophages in infected lungs showed intense intracellular staining for alpha 1Pi, associated with edema and hemorrhage.
- Activated alveolar macrophages synthesized and secreted alpha 1Pi, though in smaller amounts compared to hepatocytes.
- No significant difference in alpha 1Pi synthetic activity was found between normal and activated macrophages.
Conclusions:
- The intracellular alpha 1Pi in parasite-activated alveolar macrophages likely results from endocytosis of protease-antiprotease complexes.
- While hepatocytes are the primary source, alveolar macrophage synthesis of alpha 1Pi may offer immediate local protection within the lung's microenvironment during acute inflammation.