Expression of complement components and regulators by different subtypes of bone marrow-derived macrophages

Chang Luo1, Mei Chen, Angelina Madden

  • 1Centre for Vision and Vascular Science, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Grosvenor Road, BT12 6BA, Belfast, UK.

Inflammation
|March 28, 2012
PubMed

Insights

Macrophages exhibit distinct complement gene expression patterns during inflammation. Activated M1 and M2b macrophages show increased C3, C1INH, and CFB, suggesting a role in alternative complement pathway activation.

Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • Macrophages are key immune cells that differentiate into various functional subtypes under inflammatory conditions.
  • Complement system genes play crucial roles in immune responses and inflammation.
  • Understanding macrophage functional plasticity and its relation to complement gene expression is vital for immune research.

Purpose of the Study:

  • To investigate the constitutive and activation-dependent expression of complement-related genes in different macrophage subtypes.
  • To determine how M1, M2a, M2b, and M2c macrophage polarization affects complement gene expression profiles.
  • To elucidate the potential involvement of specific complement pathways in macrophage activation during inflammation.

Main Methods:

  • Bone marrow-derived macrophages (BMDMs) were cultured and differentiated into M0 (resting), M1, M2a, M2b, and M2c subtypes using specific stimuli (IFN-γ, LPS, IC, IL-10, IL-4).
  • Quantitative analysis of complement gene expression (including C1qb, Crry, CFH, C3, C1r, CFB, DAF1, CD59a, C2, C1INH, C1s, C4) was performed.
  • Relative expression levels were compared across different macrophage subtypes and conditions.

Main Results:

  • Constitutive expression of complement genes varied in resting BMDMs, with C1qb > Crry > CFH > C3 > C1r > CFB > DAF1 > CD59a > C2 > C1INH > C1s > C4.
  • M1 and M2b macrophages showed up-regulated expression of C1r, C1s, C3, C2, CFB, and C1INH, and down-regulated CFH, CD59a, and DAF1.
  • M2c macrophages exhibited slight up-regulation of C4 and CFH, while M2a macrophages showed weak down-regulation of complement genes compared to M0.

Conclusions:

  • Macrophage polarization significantly alters the expression of complement-related genes.
  • Elevated expression of C3, C1INH, and CFB, coupled with lower CFH in M1 and M2b macrophages, suggests their potential involvement in the alternative complement pathway during inflammation.
  • These findings highlight the intricate relationship between macrophage functional states and complement system regulation in inflammatory responses.