16
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Increased expression of FcγRI/CD64 on circulating monocytes parallels ongoing inflammation and nephritis in lupus

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          The high-affinity receptor for IgG Fcγ/CD64 is critical for the development of lupus nephritis (LN). Cross-linking Fc receptor on recruited monocytes by IgG-containing immune complexes is a key step in immune-complex-mediated nephritis in systemic lupus erythematosus (SLE). The goal of this study was to determine whether expression of Fc receptor (FcγR) I on circulating monocytes is associated with systemic inflammation and renal disease in SLE patients.

          Methods

          We studied 205 SLE patients (132 with LN and 73 without LN) along with 74 healthy control individuals. Surface expression of CD14 (monocytes), FcγRI/CD64, FcγRII/CD32, and FcγRIII/CD16 was evaluated by flow cytometry. Monocyte function was assessed by determining the migratory capacity and the ability to produce CCL2 (monocyte chemotractic protein 1). High-sensitivity C-reactive protein, C3 and C4 were measured by nephelometry.

          Results

          There was little difference in the expression of FcγRIII/CD16 or FcγRIII/CD32 on circulating monocytes between patients with SLE and control individuals. In contrast, FcγRI/CD64 expression was significantly higher in SLE patients and even higher in patients with LN. FcγRI/CD64 expression was positively associated with serum creatinine and indicators of systemic inflammation. Monocytes from patients with high FcγRI/CD64 expression also exhibited increased chemotaxis and capacity to produce monocyte chemotractic protein 1.

          Conclusions

          Increased FcγRI/CD64 expression on circulating monocytes parallels systemic inflammation and renal disease in SLE patients. We propose that circulating monocytes activated by immune complexes and/or proinflammatory mediators upregulate surface expression of FcγRI/CD64 in SLE. The enhanced chemotactic and inflammatory potential of the activated monocytes may participate in a vicious cycle of immune cell recruitment and renal injury in SLE.

          Related collections

          Most cited references50

          • Record: found
          • Abstract: found
          • Article: not found

          The CD14+ CD16+ blood monocytes: their role in infection and inflammation.

          Blood monocyte subpopulations have been defined in man initially, and the two major types of monocytes are the CD14++ CD16- and the CD14+ CD16+ monocytes. These cells have been shown to exhibit distinct phenotype and function, and the CD14+ CD16+ were labeled proinflammatory based on higher expression of proinflammatory cytokines and higher potency in antigen presentation. The current review describes these properties, including the relationship to dendritic cells, and summarizes the host of publications about CD14+ CD16+ monocytes in inflammation and infectious disease in man, all of which suggest a crucial role of these cells in the disease processes. The review also covers the more recent description of homologues of these cells in other model species, which is expected to better define the role of monocyte subsets in disease.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            IgG Fc receptors.

            Since the description of the first mouse knockout for an IgG Fc receptor seven years ago, considerable progress has been made in defining the in vivo functions of these receptors in diverse biological systems. The role of activating Fc gamma Rs in providing a critical link between ligands and effector cells in type II and type III inflammation is now well established and has led to a fundamental revision of the significance of these receptors in initiating cellular responses in host defense, in determining the efficacy of therapeutic antibodies, and in pathological autoimmune conditions. Considerable progress has been made in the last two years on the in vivo regulation of these responses, through the appreciation of the importance of balancing activation responses with inhibitory signaling. The inhibitory FcR functions in the maintenance of peripheral tolerance, in regulating the threshold of activation responses, and ultimately in terminating IgG mediated effector stimulation. The consequences of deleting the inhibitory arm of this system are thus manifested in both the afferent and efferent immune responses. The hyperresponsive state that results leads to greatly magnified effector responses by cytotoxic antibodies and immune complexes and can culminate in autoimmunity and autoimmune disease when modified by environmental or genetic factors. Fc gamma Rs offer a paradigm for the biological significance of balancing activation and inhibitory signaling in the expanding family of activation/inhibitory receptor pairs found in the immune system.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              C-reactive protein: ligands, receptors and role in inflammation.

              C-reactive protein (CRP) is the prototypical acute phase serum protein, rising rapidly in response to inflammation. CRP binds to phosphocholine (PC) and related molecules on microorganisms and plays an important role in host defense. However, a more important role may be the binding of CRP to PC in damaged membranes. CRP increases clearance of apoptotic cells, binds to nuclear antigens and by masking autoantigens from the immune system or enhancing their clearance, CRP may prevent autoimmunity. CRP binds to both the stimulatory receptors, FcgammaRI and FcgammaRIIa, increasing phagocytosis and the release of inflammatory cytokines; and to the inhibitory receptor, FcgammaRIIb, blocking activating signals. We have shown that, in two animal models of systemic lupus erythematosus (SLE), the (NZB x NZW)F1 mouse and the MRL/lpr mouse, a single injection of CRP before onset of proteinuria delayed disease development and late treatment reversed proteinuria. Thus, in these models, CRP plays an anti-inflammatory role.
                Bookmark

                Author and article information

                Journal
                Arthritis Res Ther
                Arthritis Research & Therapy
                BioMed Central
                1478-6354
                1478-6362
                2009
                14 January 2009
                : 11
                : 1
                : R6
                Affiliations
                [1 ]Division of Rheumatology & Clinical Immunology, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610-0221, USA
                [2 ]Division of Nephrology, Hypertension and Transplantation, Department of Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610-0221, USA
                [3 ]Schering-Plough Corporation, Kenilworth, NJ 07033-0530, USA
                Article
                ar2590
                10.1186/ar2590
                2688236
                19144150
                b3cc4f45-63b8-4776-8fd2-8887446656a9
                Copyright © 2009 Li et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 August 2008
                : 24 October 2008
                : 21 November 2008
                : 14 January 2009
                Categories
                Research Article

                Orthopedics
                Orthopedics

                Comments

                Comment on this article