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Alveolar macrophage-derived chemotactic factor: kinetics of in vitro production and partial characterization
Abstract:
Alveolar macrophages are the initial phagocytic cells that encounter foreign material and particulates deposited in the terminal airways. We have examined a mechanism by which these cells, after phagocytic challenge, may control or amplify the inflammatory response in lung parenchyma. Normal human alveolar macrophages (AM) were studied from eight subjects. With in vitro culture, AM produced and released two substances into culture media which have potent chemoattractant activity for blood polymorphonuclear granulocytes (PMN) and negligible activity for mononuclear cells. Release of these factors is maximally stimulated by aggregated human immunoglobulin (Ig)G or zymosan particles; however, simple adhesion of the macrophages to plastic surfaces is also sufficient to stimulate release of these chemotactic substances. The larger substance (10,000 daltons) is immunologically distinct from C5a and interacts with a different PMN membrane receptor than that known to exist for formyl-methionyl-leucyl-phenylalanine. Its chemotactic activity is sensitive to the enzymatic effect of trypsin. Although producing a single elution peak on gelfiltration chromatography, electrofocusing in polyacrylamide gels yielded five peaks of radioactivity. Chemotactic activity was localized to a fraction with a pI = 5.0. The smaller molecular weight substance has been less well characterized. Thus, the human AM can produce at least two factors which attract PMN and this capability may augment the local inflammatory response in the lung.
Insights
Human alveolar macrophages (AM) release two substances that attract polymorphonuclear granulocytes (PMN), potentially amplifying lung inflammation after encountering foreign materials. This finding offers insights into immune responses in the airways.
Area of Science:
- Pulmonary immunology
- Cellular biology
- Inflammation research
Background:
- Alveolar macrophages (AM) are crucial phagocytic cells in the lung's terminal airways.
- These cells encounter inhaled foreign materials and particulates.
- Understanding AM's role in modulating inflammatory responses is vital for lung health.
Purpose of the Study:
- To investigate the mechanisms by which alveolar macrophages control or amplify lung inflammation.
- To identify substances released by human AM that influence inflammatory cell recruitment.
Main Methods:
- In vitro culture of normal human alveolar macrophages (AM) from eight subjects.
- Stimulation of AM with aggregated human immunoglobulin (Ig)G or zymosan particles.
- Characterization of released chemoattractant substances using gel filtration, electrofocusing, and enzymatic sensitivity assays.
Main Results:
- AM produced and released two chemoattractant substances for blood polymorphonuclear granulocytes (PMN).
- Release was stimulated by aggregated IgG, zymosan, or simple macrophage adhesion.
- The larger substance (10,000 daltons) is distinct from C5a and interacts with a different PMN receptor.
Conclusions:
- Human alveolar macrophages produce at least two factors that attract PMN.
- This capability can augment local inflammatory responses in the lung parenchyma.
- Further characterization of these factors may reveal therapeutic targets for inflammatory lung diseases.
