Elastolytic activity of peripheral blood monocytes.

Area of Science:

• Immunology
• Biochemistry
• Cell Biology

Background:

• Human peripheral blood monocytes exhibit elastolytic activity.
• Neutrophils also possess elastolytic enzymes, but monocytes are a principal source.
• The role of monocyte-derived elastases in physiological and pathological processes is under investigation.

Purpose of the Study:

• To quantify and characterize the elastolytic activity of human peripheral blood monocytes.
• To compare the elastolytic activity of monocytes with that of neutrophils and lymphocytes.
• To investigate the enzymatic nature and molecular forms of monocyte elastolytic activity.

Main Methods:

• Purification of human peripheral blood monocytes using Ficoll-Hypaque density gradient centrifugation and plastic adherence.
• Assay of elastolytic activity using insoluble [3H]elastin.
• Inhibition studies with alpha-1-antitrypsin and a serine protease inhibitor (Succinyl-Ala-Ala-Pro-Val-chloromethylketone).
• Gel filtration chromatography of monocyte and neutrophil extracts.

Main Results:

• Monocytes solubilize 5-10 micrograms of elastin per mg protein per hour at pH 7.5.
• Monocyte elastolytic specific activity is 3-15% of that of neutrophils.
• The activity is primarily derived from monocytes, with lymphocytes showing trace activity.
• Monocyte elastolytic activity is sensitive to alpha-1-antitrypsin and a specific serine protease inhibitor, indicating it's a serine protease.
• Gel filtration revealed large molecular weight forms of elastolytic activity in monocyte extracts, differing from lysosomal extracts.

Conclusions:

• Human peripheral blood monocytes are a significant source of elastolytic activity.
• This activity is attributed to a serine protease.
• Monocytes contribute to elastolytic processes in various organs, including the lungs, during both normal and disease states.