| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Laboratory for Cellular and Molecular Immunology, Department of Medicine, Hadassah University Hospital, Jerusalem, Israel;
Sourasky Medical Center, Tel-Aviv, Israel; and
Immunology Unit, Bney-Zion Hospital, Haifa, Israel
Impaired handling of apoptotic cells has been suggested as an important factor in the development of systemic lupus erythematosus (SLE), and a role for complement in the removal of apoptotic cells was shown recently. We studied the in vitro function of macrophages from 40 patients with SLE and their matched controls in the removal of heterologous apoptotic cells opsonized by iC3b. Interaction index of apoptotic cells opsonized by iC3b was significantly lower in patients with SLE and averaged 71% ± 37 of that of healthy individuals (p < 0.002) and 69% ± 35 of patients with rheumatoid arthritis (p < 0.007). SLE patients had increased apoptosis of both freshly isolated monocytes (p < 0.001) and maturing macrophages (p < 0.04) that led to decreased density of monocyte-derived macrophages. Apoptosis was inhibited by adding soluble Fas receptor indicating Fas-mediated apoptosis. As demonstrated in both healthy controls and patients with SLE, decreased macrophage density by itself caused significant decreased uptake of apoptotic cells by the remaining macrophages. Maintaining normal density in SLE patients either by an increased initial density or by using soluble Fas restored the interaction capacity of the individual macrophages in the majority of patients. We concluded that impaired in vitro interaction of iC3b-opsonized apoptotic cells with macrophages from patients with SLE was mainly associated with Fas-dependent accelerated apoptosis of the monocytes/macrophages. Accelerated apoptosis of phagocytes may represent a novel in vitro mechanism of impairment of interaction with apoptotic cells that, apart from reducing the number of professional phagocytes, alters the function of the remaining macrophages.
This article has been cited by other articles:
|
|
 |
|
  E. Tinazzi, A. Puccetti, R. Gerli, A. Rigo, P. Migliorini, S. Simeoni, R. Beri, M. Dolcino, N. Martinelli, R. Corrocher, et al. Serum DNase I, soluble Fas/FasL levels and cell surface Fas expression in patients with SLE: a possible explanation for the lack of efficacy of hrDNase I treatment Int. Immunol., March 1, 2009; 21(3): 237 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Burdo, M. R. Wood, and H. S. Fox Osteopontin prevents monocyte recirculation and apoptosis J. Leukoc. Biol., June 1, 2007; 81(6): 1504 - 1511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Krispin, Y. Bledi, M. Atallah, U. Trahtemberg, I. Verbovetski, E. Nahari, O. Zelig, M. Linial, and D. Mevorach Apoptotic cell thrombospondin-1 and heparin-binding domain lead to dendritic-cell phagocytic and tolerizing states Blood, November 15, 2006; 108(10): 3580 - 3589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Denny, P. Chandaroy, P. D. Killen, R. Caricchio, E. E. Lewis, B. C. Richardson, K.-D. Lee, J. Gavalchin, and M. J. Kaplan Accelerated Macrophage Apoptosis Induces Autoantibody Formation and Organ Damage in Systemic Lupus Erythematosus J. Immunol., February 15, 2006; 176(4): 2095 - 2104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S W Tas, P Quartier, M Botto, and L Fossati-Jimack Macrophages from patients with SLE and rheumatoid arthritis have defective adhesion in vitro, while only SLE macrophages have impaired uptake of apoptotic cells Ann Rheum Dis, February 1, 2006; 65(2): 216 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Bijl, E Reefman, G Horst, P C Limburg, and C G M Kallenberg Reduced uptake of apoptotic cells by macrophages in systemic lupus erythematosus: correlates with decreased serum levels of complement Ann Rheum Dis, January 1, 2006; 65(1): 57 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Koller, B. Zwolfer, G. Steiner, J. S. Smolen, and C. Scheinecker Phenotypic and functional deficiencies of monocyte-derived dendritic cells in systemic lupus erythematosus (SLE) patients Int. Immunol., November 1, 2004; 16(11): 1595 - 1604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C C Mok and C S Lau Pathogenesis of systemic lupus erythematosus J. Clin. Pathol., July 1, 2003; 56(7): 481 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Moosig, D. Graf, A. Knorr-Spahr, R. A Zeuner, S. Bottcher, J. O Schroder, J. Jimenez-Alonso, D. Esteva, C. Vera, J. M. Sabio, et al. Letter to the Editor Lupus, June 1, 2003; 12(6): 490 - 493. [PDF]
|
|
|
|
 |
|
 I. Ferreiros-Vidal, J. Garcia-Meijide, P. Carreira, F. Barros, A. Carracedo, J. J. Gomez-Reino, and A. Gonzalez The three most common CARD15 mutations associated with Crohn's disease and the chromosome 16 susceptibility locus for systemic lupus erythematosus Rheumatology, April 1, 2003; 42(4): 570 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Potter, J. Cortes-Hernandez, P. Quartier, M. Botto, and M. J. Walport Lupus-Prone Mice Have an Abnormal Response to Thioglycolate and an Impaired Clearance of Apoptotic Cells J. Immunol., March 15, 2003; 170(6): 3223 - 3232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F Silvestris, D Grinello, M Tucci, P Cafforio, and F Dammacco Enhancement of T cell apoptosis correlates with increased serum levels of soluble Fas (CD95/Apo-I) in active lupus Lupus, January 1, 2003; 12(1): 8 - 14. [Abstract] [PDF]
|
|
|
|
|
|
J. Wu, C. Metz, X. Xu, R. Abe, A. W. Gibson, J. C. Edberg, J. Cooke, F. Xie, G. S. Cooper, and R. P. Kimberly A Novel Polymorphic CAAT/Enhancer-Binding Protein {beta} Element in the FasL Gene Promoter Alters Fas Ligand Expression: A Candidate Background Gene in African American Systemic Lupus Erythematosus Patients J. Immunol., January 1, 2003; 170(1): 132 - 138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Verbovetski, H. Bychkov, U. Trahtemberg, I. Shapira, M. Hareuveni, O. Ben-Tal, I. Kutikov, O. Gill, and D. Mevorach Opsonization of Apoptotic Cells by Autologous iC3b Facilitates Clearance by Immature Dendritic Cells, Down-regulates DR and CD86, and Up-regulates CC Chemokine Receptor 7 J. Exp. Med., December 16, 2002; 196(12): 1553 - 1561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J W. Dieker, J van der Vlag, and J H. Berden Triggers for anti-chromatin autoantibody production in SLE Lupus, December 1, 2002; 11(12): 856 - 864. [Abstract] [PDF]
|
|
|
|
|
|
M. J. Kaplan, E. E. Lewis, E. A. Shelden, E. Somers, R. Pavlic, W. J. McCune, and B. C. Richardson The Apoptotic Ligands TRAIL, TWEAK, and Fas Ligand Mediate Monocyte Death Induced by Autologous Lupus T Cells J. Immunol., November 15, 2002; 169(10): 6020 - 6029. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
