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Chemotactic and mitogenic components of the alveolar macrophage response to particles ad neutrophil chemoattractant
Abstract:
The pulmonary response to instilled particulates involves initial efflux of polymorphonuclear leukocytes (PMNs) and increased production of alveolar macrophages (AMs). The relationships of the cell migration and division components of the AM production to the initial PMN response after intrapulmonary carbon or latex administration are examined. Supernatants of lung lavages taken during early PMN migration to the alveoli promote sequential migration of PMNs, migration of monocytes, and division of pulmonary interstitial cells in normal mice. Supernatants taken during the phase of increased cell division in the lung produce no such effects, implying tht factors responsible for chemotaxis and mitosis are generated rapidly and are short-lived. A possible source is the interaction of AMs with particles, since supernatants of such incubations induce an inflammatory response in vivo. Similarly, when a synthetic chemoattractant is used, efflux of PMNs is followed by macrophages arising from migration of monocytes and from division of interstitial cells. The results suggest that particulate instillation in the lung stimulates a standard inflammatory response in which rapid generation of a factor(s) chemotactic for PMNs also attracts mononuclear cells to the alveoli. The initial efflux of cells may be explained by migration from the blood, but continued demand or replacement requires mitotic activity of precursors. For the alveolar macrophages, this includes division of cells in the pulmonary interstitium.
Insights
Particulate inhalation triggers an inflammatory response in the lungs, involving polymorphonuclear leukocytes (PMNs) and alveolar macrophages (AMs). Factors attracting these cells are rapidly generated and short-lived, originating from macrophage-particle interactions.
Area of Science:
- Pulmonary immunology
- Cellular biology
- Inflammation research
Background:
- Pulmonary exposure to particulates initiates an inflammatory cascade.
- This response involves polymorphonuclear leukocytes (PMNs) and alveolar macrophages (AMs).
Purpose of the Study:
- To investigate the relationship between PMN response and alveolar macrophage production.
- To understand the roles of cell migration and division in AM generation following particulate exposure.
Main Methods:
- Administration of carbon or latex particles into the lungs of mice.
- Analysis of lung lavage fluid supernatants.
- In vitro incubation of alveolar macrophages with particles.
- Use of synthetic chemoattractants.
Main Results:
- Lung lavage supernatants from early PMN migration phases induced PMN migration, monocyte migration, and interstitial cell division.
- Supernatants from later phases (increased cell division) lacked these effects, suggesting short-lived factors.
- Alveolar macrophage-particle interactions produced supernatants that induced inflammation in vivo.
- Chemoattractant-induced PMN efflux was followed by macrophage recruitment via monocyte migration and interstitial cell division.
Conclusions:
- Particulate instillation triggers a rapid inflammatory response involving chemotactic factors for PMNs and mononuclear cells.
- These factors are short-lived, indicating rapid generation and clearance.
- Alveolar macrophage replenishment relies on monocyte migration and interstitial cell proliferation, particularly division of pulmonary interstitial cells.