The role of macrophages in the rheumatic diseases
In this article the functions of the macrophage are reviewed and a role for the macrophage in rheumatic disease is proposed. The known mechanisms by which mononuclear phagocytes are mobilised from the bone marrow as a result of peripheral macrophages making contact with antigen are outlined. The mechanisms of macrophage accumulation at sites of antigen presence are summarised with emphasis being placed upon the inflammatory mediators derived from the complement cascade. The importance of Hageman factor in converting the plasma proenzymes, pre-plasma thromboplastin antecedent (pre-PTA), plasminogen proactivator and pre-kallikrein are emphasised. The fact that macrophages themselves produce a proteinase which can cleave C5 with chemotactic activity release is a mechanism for amplification of phagocyte accumulation. In addition lymphocytes when stimulated can produce lymphokines that similarly cause accumulation of mononuclear cells at sites of delayed hypersensitivity. The role of the macrophage in antigen processing is outlined including the importance of the production of 'super antigen' by complexing with RNA and the various physical interactions which can occur between macrophages and lymphocytes which may lead to augmentation of the immune response are discussed. The role of the macrophage as a secretory cell is emphasised and the various hydrolases, prostaglandins and immuno-regulatory products are described. These functional attributes of the macrophage are proposed as being of importance in the production of the chronic synovitis characteristic of the various inflammatory arthritides. If the antigen of importance in the production of synovial inflammation were non-degradable a hyper-inflammatory response with a chronic time course could result.
