Modulation of monocyte complement synthesis by lymphocytes and lymphocyte-conditioned media

Area of Science:

• Immunology
• Complement System Biology

Background:

• Peripheral blood lymphocytes (PBL) and synovial membrane lymphocytes (SML) modulate monocyte complement synthesis.
• Rheumatoid arthritis SML can stimulate C2 synthesis without mitogens/antigens.

Purpose of the Study:

• To investigate the role of lymphocytes and their products in modulating monocyte complement component C2 synthesis.
• To identify the specific lymphocyte-derived factors responsible for this modulation.
• To explore the functional characteristics of monocyte-derived C2.

Main Methods:

• Culture supernatants from stimulated human PBL and SML were used to treat human monocytes.
• Depletion of lymphocyte populations (B and T cells) to identify stimulatory cells.
• Measurement of synthesis rates for complement components (C2, C3, Factor B, C1 inhibitor, Properdin).
• Use of recombinant gamma-interferon (rIFN-gamma) and anti-IFN-gamma antibodies.
• Assay of specific functional activity (SpFA) of C2.

Main Results:

• Lymphocytes and their supernatants stimulated monocyte C2, Factor B, and C1 inhibitor synthesis, while reducing C3 and Properdin.
• T cells were identified as the primary stimulators of C2 synthesis.
• The observed effects mimicked those of rIFN-gamma, suggesting IFN-gamma as a key mediator.
• A second lymphocyte product was found to further increase the specific functional activity (SpFA) of monocyte-derived C2, an 'oxidation' effect.
• Monocyte-derived C2 exhibited higher SpFA and formed a more stable C3 convertase compared to serum or HepG2-derived C2.

Conclusions:

• Gamma-interferon is a major lymphocyte product that modulates monocyte complement synthesis.
• A second, unidentified lymphocyte factor contributes to the 'oxidation' of monocyte C2.
• The production of 'oxidized' C2 by monocytes, enhanced by lymphocytes/IFN-gamma, may perpetuate inflammation in conditions like rheumatoid arthritis.