Human pulmonary macrophage-derived mucus secretagogue

Area of Science:

• Immunology
• Pulmonary Medicine
• Cell Biology

Background:

• Human pulmonary macrophages (PM) play a role in lung immune responses.
• Mucus hypersecretion is a hallmark of various airway diseases.

Purpose of the Study:

• To identify and characterize a factor released by activated human PM that influences mucus secretion.
• To investigate the nature and properties of this newly discovered secretagogue.

Main Methods:

• Human lung tissue was used to isolate pulmonary macrophages.
• Macrophages were exposed to activated zymosan, and released factors were collected.
• Cultured human airways were used to assess the effect of the factor on mucous glycoprotein release.
• Physicochemical properties of the factor were determined through sequential fractionation and analysis.

Main Results:

• Activated PM released a factor, termed macrophage-derived mucus secretagogue (MMS), which increased mucous glycoprotein release from airways.
• MMS release was dose-dependent and triggered by C3-dependent and Fc receptor-mediated activation of PM.
• MMS is a small (approx. 2000 Da), acidic (pI 5.15) molecule, not derived from arachidonic acid.
• MMS synthesis was sensitive to cycloheximide, indicating de novo protein synthesis.

Conclusions:

• Surface activation of human PM leads to the synthesis and release of a novel small, acidic molecule (MMS).
• MMS stimulates airway mucous glands to increase mucous glycoprotein secretion.
• This finding provides a new molecular link between immune cell activation and mucus production in the airways.