Macrophage Depletion Prevents Leukocyte Adhesion and Disease Induction in Experimental Melanin-protein Induced Uveitis

Baatz, H.; Puchta, Joachim; Reszka, Regina; Pleyer, Uwe

doi:10.1006/exer.2001.1016

Cited by 17 publications

(7 citation statements)

References 14 publications

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“…Additional studies have shown that clodronate administration causes significant decreases of marginal zone M as well as red pulp M within 24 h, and thereafter, these areas gradually repopulate to even higher levels than before the injection (28,34,(83)(84)(85)(86). Furthermore, tissue M in the lungs and kidneys are not depleted (33).…”

Section: Discussionmentioning

confidence: 98%

Accelerated Macrophage Apoptosis Induces Autoantibody Formation and Organ Damage in Systemic Lupus Erythematosus

Denny¹,

Chandaroy²,

Killen

et al. 2006

The Journal of Immunology

112

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Increased monocyte/macrophage (Mφ) apoptosis occurs in patients with systemic lupus erythematosus (SLE) and is mediated, at least in part, by an autoreactive CD4+ T cell subset. Furthermore, autoreactive murine CD4+ T cells that kill syngeneic Mφ in vitro induce a lupus-like disease in vivo. However, it is unclear whether increased Mφ apoptosis in SLE per se is sufficient to accelerate/promote autoimmunity. We have investigated whether increased Mφ apoptosis in vivo, induced by the administration of clodronate liposomes, can exacerbate the autoimmune phenotype in NZB × SWR (SNF1) lupus-prone mice, and induce autoantibody production in haplotype-matched BALB/c × DBA1 (DBF1) non-lupus-prone mice. Lupus-prone mice SNF1 mice that were treated with clodronate liposomes, but not mice treated with vehicle, developed significant increases in autoantibodies to dsDNA, nucleosomes, and the idiotypically related family of nephritic Abs IdLNF1, when compared with untreated SNF1 mice. Furthermore, clodronate treatment hastened the onset of proteinuria and worsened SNF1 lupus nephritis. When compared with vehicle-treated controls, clodronate-treated non-lupus-prone DBF1 mice developed significantly higher levels of anti-nucleosome and IdLNF1 Abs but did not develop lupus nephritis. We propose that Mφ apoptosis contributes to the pathogenesis of autoantibody formation and organ damage through both an increase in the apoptotic load and impairment in the clearance of apoptotic material. This study suggests that mechanisms that induce scavenger cell apoptosis, such as death induced by autoreactive cytotoxic T cells observed in SLE, could play a pathogenic role and contribute to the severity of the disease.

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Section: Discussionmentioning

confidence: 98%

Accelerated Macrophage Apoptosis Induces Autoantibody Formation and Organ Damage in Systemic Lupus Erythematosus

Denny¹,

Chandaroy²,

Killen

et al. 2006

The Journal of Immunology

112

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“…Marked attenuation of macrophage infiltration will reduce TNF-␣ release locally and its direct cytotoxic effects on renal epithelial cells. In experimental uveitis, macrophage depletion with Cl 2 MBP reduced leukocyte rolling, arrest, and emigration, as well as plasma TNF-␣ levels (2). Activation of macrophages requires exposure to IFN-␥ (17).…”

Section: Role Of Macrophages In Irimentioning

confidence: 98%

“…Other animal models provide some insight into the potential role of macrophages. In experimental uveitis, liposomal dichloromethylene-diphosphonate depleted macrophages and prevented leukocyte-endothelial cell interaction, thus providing evidence for the central role of macrophages in this form of inflammation (2). In arterial injury, macrophage depletion using liposomal clodronate reduced inflammation involved in neointimal hyperplasia (8).…”

Section: Role Of Macrophages In Irimentioning

confidence: 98%

Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages

Day¹,

Huang²,

Zhang³

et al. 2005

American Journal of Physiology-Renal Physiology

264

210

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The role of monocytes/macrophages in the pathogenesis of ischemia-reperfusion injury (IRI) is unknown. We sought to determine whether activation of macrophage adenosine 2A (A(2A)) receptors (A(2A)Rs) mediates tissue protection. We subjected C57Bl/6 mice infused with clodronate [dichloromethylene bisphosphonate (Cl(2)MBP)] to IRI (32 min of ischemia followed by 24 h of reperfusion) to deplete them of macrophages. IRI induced an elevation of plasma creatinine that was reduced with Cl(2)MBP (26% of control). Adoptive transfer of murine RAW 264.7 cells reconstituted injury, an effect blocked significantly by A(2A) agonists (27% of plasma creatinine from mice reconstituted with macrophages). Macrophages subjected to A(2A) knockout by small interfering RNA were adoptively transferred to macrophage-depleted mice and reconstituted injury (110% of control mice); however, the increase in plasma creatinine was blocked by A(2A) agonists (20% of vehicle treatment). Finally, the A(2A) agonist effect on IRI was blocked in macrophage-depleted A(2A)-knockout mice reconstituted with wild-type RAW 264.7 cells. RNase protection assays 24 h after IRI demonstrated that macrophages are required for IL-6 and TGF-beta mRNA induction. However, A(2A) agonist-mediated tissue protection is independent of IL-6 and TGF-beta mRNA. We conclude that the full extent of IRI requires macrophages and that A(2A) agonist-mediated tissue protection is independent of activation of macrophage A(2A)Rs.

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“…The response is dependent on the timing of administration relative to challenge with the exciting stimulus. 7,8 These findings would suggest that non-nitrobisphosphonates might be safer for patients with a history of uveitis. Even use of this class of drugs, however, warrants caution, as shown in a recent report of uveitis induced by clodronate and confirmed on rechallenge.…”

Section: Discussionmentioning

confidence: 93%

Corneal Graft Rejection Precipitated by Uveitis Secondary to Alendronate Sodium Therapy

Richards¹,

Wiffen²

2006

Cornea

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Macrophage Depletion Prevents Leukocyte Adhesion and Disease Induction in Experimental Melanin-protein Induced Uveitis

Cited by 17 publications

References 14 publications

Accelerated Macrophage Apoptosis Induces Autoantibody Formation and Organ Damage in Systemic Lupus Erythematosus

Accelerated Macrophage Apoptosis Induces Autoantibody Formation and Organ Damage in Systemic Lupus Erythematosus

Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages

Corneal Graft Rejection Precipitated by Uveitis Secondary to Alendronate Sodium Therapy

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