From: Cells of the synovium in rheumatoid arthritis. Macrophages
Function | Mechanisms | (Potential) role in rheumatoid arthritis |
---|---|---|
Clearance of immune complexes | Binding of immunoglobulins to Fc receptors (Fc-γ-R I, IIA, IIB, and IIIA) | Potential clearance of rheumatoid factor but further activation of monocytes/Mφ |
 |  | Opsonization of complexes by complement, leading to binding to Mφ complement receptors and further cell activation [101,102] (reviewed in [2,103]) |
 |  | Notably, inhibition of monocyte activation by Fc-γ-R IIB [102] |
Complement activation | Binding of complement factors to complement receptors 1 (CD35), 3 (CD11b), and 5a (CD88) | Recognition of activated complement (soluble phase or on immunoglobulin G-immune complexes) |
 |  | Promotion of phagocytosis and activation of monocytes/Mφ [103] |
Phagocytosis of particulate antigens | Conventional (Fc-mediated) → lysosomal degradation and MHC-II antigen processing | Scavenging of debris but potential import of arthritogenic molecules [103] |
 |  | Antigen presentation and activation of CD4+ and CD8+ T cells, possibly relevant to disease initiation or perpetuation (spreading of autoimmunity) (reviewed in [2]) |
 | Coiling phagocytosis → lysosomal degradation and MHC-I antigen processing | Involved in phagocytosis of Borrelia burgdorferi, active agent of Lyme arthritis (reviewed in [2]) |
Clearance of intracellular pathogens and apoptotic cells | Removal of pathogens and recognition of apoptotic cells via exposed intracellular membrane components | Induction of Mφ-derived cytokines by bacterial toxins or superantigens [26,28,103] |
 |  | Modulation of Mφ responses by mycobacterial lipoarabinomannan [104,105] or Toll-like receptors [29,106] |
 |  | Persistence of obligate/facultative intracellular pathogens with arthritogenic potential [107,108] |
Antigen processing and presentation | Enzymatic degradation of antigens and binding of antigenic peptides to MHC molecules and transport to the cell surface | Important cognate functions upon antigen recognition via presentation of antigen on MHC-II molecules [109] and expression of membrane second signal molecules adjacent to T cells (reviewed in [2]) |
Chemotaxis and angiogenesis | Attraction of other inflammatory cells and induction of neo-vascularization | Positive feedback between Mφ-derived cytokines and chemotactic factors (for example, IL-8 and monocyte chemoattractant protein-1) Promotion of angiogenesis by IL-8 and soluble forms of adhesion molecules (for example, vascular cell adhesion molecule-1 and endothelial-leukocyte adhesion molecule-1) [69] |
Wound healing | Remodelling of tissue via interaction with fibroblasts | Sustained monocyte recruitment at wound injury sites via monocyte chemoattractant macrophage inflammatory protein-1α Phagocytosis of matrix debris and endogenous production of IL-1, TNF-α, and so on as well as post-injury tissue remodelling (reviewed in [2]) |
Lipid metabolism | Mφ synthesis of prostaglandins (PGs) E2 and I2 Expression of scavenger receptor A (uptake of oxidized low-density lipoprotein) | Pro-inflammatory activity of PGE2 and PGI2 and leukotrienes in rheumatoid arthritis, but also autocrine negative feedback through peroxisome proliferator-activated receptors α and γ (reviewed in [2]) Fish-based diets are associated with clinical improvement of human and experimental arthritis (reviewed in [2]) |
 |  | Modulation of T cell-contact-induced production of IL-1β and TNF-α in Mφ by apolipoprotein A-I [110] |