Serum amyloid A: evidence for its origin in polymorphonuclear leukocytes

Area of Science:

• Immunology
• Hematology
• Biochemistry

Background:

• Amyloid A is a protein fragment associated with amyloidosis.
• The cellular source and production mechanisms of amyloid A are not fully understood.

Purpose of the Study:

• To investigate the presence and production of amyloid A-related material in human leukocyte subpopulations.
• To determine which leukocyte type is responsible for amyloid A production and release.

Main Methods:

• Isolation of human leukocyte subpopulations (monocytes, granulocytes, lymphocytes) using Ficoll-Hypaque gradients and cell separation techniques.
• Culture of isolated leukocytes and measurement of amyloid A content in cell sonicates and culture medium using radioimmunoassay.
• Assessment of the effects of various inhibitors (colchicine, vincristine, puromycin, cycloheximide) on amyloid A production and release.

Main Results:

• Granulocytes contained significantly higher levels of amyloid A-related material compared to serum levels.
• Mononuclear leukocyte subpopulations showed negligible amyloid A content.
• Amyloid A content increased in cultured granulocytes, peaking between 16-30 hours.
• Granulocyte release of amyloid A into the medium was observed in some individuals and could be blocked by inhibitors.
• Intracellular increase of amyloid A in granulocytes was inhibited by puromycin and cycloheximide.

Conclusions:

• Human granulocytes are a significant source of amyloid A antigenically related material.
• Granulocytes produce and can release amyloid A, with production influenced by protein synthesis and potentially other cellular processes.
• The exact conditions and triggers for granulocyte-mediated amyloid A release require further investigation.