Objectives: To review current developments, regarding the
pathophysiologic role of monocytes and macrophages in systemic lupus
erythematosus (SLE).
Methods: We searched Medline for articles written in the English
language using the following terms: monocyte(s) or macrophage(s) and
lupus. Although our search spanned the years 1971 to 2008, the majority
of the short-listed articles belonged to the period 2000 to 2008.
Published literature on phenotypic and functional properties of
monocytes/macrophages (Mo/M phi) in SLE was reviewed. References from
identified articles were also selected. Currently available experimental
data and their relevance to the pathogenesis of SLE are critically
discussed.
Results: It has traditionally been held that impaired phagocytosis by
monocytes and macrophages in SLE allows for the accumulation of
apoptotic debris leading to a sequel of autoimmune phenomena. Recent
paradigms derived from animal models of systemic autoimmunity, however,
has broadened our understanding regarding the possible pathophysiologic
roles of Mo/M phi in SLE. Data derived from studies in patients with SLE
show multiple aberrations in activation status and secretory functions
of circulating and tissue-infiltrating Mo/M phi. Such aberrations may be
associated with dysregulation of T-cell function and autoantibody
production in SLE. Moreover, emerging evidence suggests that phagocytic
capacity and antigen-presenting properties of Mo/M phi are enhanced in
some patients with SLE.
Conclusions: While defective phagocytosis represents a distinctive
feature of monocyte function in some patients with SLE, aberrant
activation of the Mo/M phi system may be a more appropriate concept to
encompass the broad spectrum of Mo/M phi disorders in SLE. Aberrant
function of lupus Mo/M phi appears to play a dynamic role in the
initiation and perpetuation of the systemic autoimmune response and
organ damage. Delineation of the altered biology of lupus Mo/M phi could
provide possible future therapeutic targets for patients with SLE. 2010
Elsevier Inc. All rights reserved. Semin Arthritis Rheum 39:491-50
