Table 3

Monocyte/macrophage functions and their (potential) role in rheumatoid arthritis

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]


IL, interleukin; Mφ, macrophage(s); MHC, major histocompatibility complex; TNF-α, tumor necrosis factor-alpha. Reproduced with permission from Kinne RW, Stuhlmuller B, Palombo-Kinne E, Burmester GR: The role of macrophages in rheumatoid arthritis. In Rheumatoid Arthritis. Edited by Firestein GS, Panayi GS, Wollheim FA. New York: Oxford University Press; 2006:55–75 [2].

Kinne et al. Arthritis Research & Therapy 2007 9:224   doi:10.1186/ar2333