Liposomes for Specific Depletion of Macrophages from Organs and Tissues

Rooijen, Nico van; Hendrikx, Esther M. L.

doi:10.1007/978-1-60327-360-2_13

Cited by 327 publications

(316 citation statements)

References 27 publications

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“…Phagocytic uptake of liposome-encapsulated clodronate (Clo-Lipo) is a well-established method for specific in vivo ablation of macrophages (24). This reagent was effective in specifically depleting circulating axolotl monocytes and tissue resident macrophages on i.v.…”

Section: Mononuclear Phagocytes Regulate Regenerative Gene Expressionmentioning

confidence: 99%

Macrophages are required for adult salamander limb regeneration

Godwin

Pinto

Rosenthal

2013

Proc. Natl. Acad. Sci. U.S.A.

719

767

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The failure to replace damaged body parts in adult mammals results from a muted growth response and fibrotic scarring. Although infiltrating immune cells play a major role in determining the variable outcome of mammalian wound repair, little is known about the modulation of immune cell signaling in efficiently regenerating species such as the salamander, which can regrow complete body structures as adults. Here we present a comprehensive analysis of immune signaling during limb regeneration in axolotl, an aquatic salamander, and reveal a temporally defined requirement for macrophage infiltration in the regenerative process. Although many features of mammalian cytokine/chemokine signaling are retained in the axolotl, they are more dynamically deployed, with simultaneous induction of inflammatory and anti-inflammatory markers within the first 24 h after limb amputation. Systemic macrophage depletion during this period resulted in wound closure but permanent failure of limb regeneration, associated with extensive fibrosis and disregulation of extracellular matrix component gene expression. Full limb regenerative capacity of failed stumps was restored by reamputation once endogenous macrophage populations had been replenished. Promotion of a regeneration-permissive environment by identification of macrophage-derived therapeutic molecules may therefore aid in the regeneration of damaged body parts in adult mammals.

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Section: Mononuclear Phagocytes Regulate Regenerative Gene Expressionmentioning

confidence: 99%

Macrophages are required for adult salamander limb regeneration

Godwin

Pinto

Rosenthal

2013

Proc. Natl. Acad. Sci. U.S.A.

719

767

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“…to selectively ablate macrophages in a variety of systems, including the inner ear (Van Rooijen and Sanders 1994;van Rooijen et al 1996;van Rooijen and Hendrikx 2010;Warchol et al 2012). We first examined the effect of LC on macrophage survival by treating utricles from CX3CR1 GFP/+ mice, which express GFP exclusively in macrophages in the inner ear (Hirose et al 2005).…”

Section: Fig 2 Ho-1 Protects Against Cisplatin-induced Hair Cell Dementioning

confidence: 99%

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

Baker

Roy

Brandon

et al. 2014

JARO

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Cisplatin is a highly successful and widely used chemotherapy for the treatment of various solid malignancies in both adult and pediatric patients. Side effects of cisplatin treatment include nephrotoxicity and ototoxicity. Cisplatin ototoxicity results from damage to and death of cells in the inner ear, including sensory hair cells. We showed previously that heat shock inhibits cisplatin-induced hair cell death in whole-organ cultures of utricles from adult mice. Since heat shock protein 70 (HSP70) is the most upregulated HSP in response to heat shock, we investigated the role of HSP70 as a potential protectant against cisplatin-induced hair cell death. Our data using utricles from HSP70 −/− mice indicate that HSP70 is necessary for the protective effect of heat shock against cisplatin-induced hair cell death. In addition, constitutive expression of inducible HSP70 offered modest protection against cisplatin-induced hair cell death. We also examined a second heat-inducible protein, heme oxygenase-1 (HO-1, also called HSP32). HO-1 is an enzyme responsible for the catabolism of free heme. We previously showed that induction of HO-1 using cobalt protoporphyrin IX (CoPPIX) inhibits aminoglycoside-induced hair cell death. Here, we show that HO-1 also offers significant protection against cisplatin-induced hair cell death. HO-1 induction occurred primarily in resident macrophages, with no detectable expression in hair cells or supporting cells. Depletion of macrophages from utricles abolished the protective effect of HO-1 induction. Together, our data indicate that HSP induction protects against cisplatin-induced hair cell death, and they suggest that resident macrophages mediate the protective effect of HO-1 induction.

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“…The first involved the intravenous injection of liposomeencapsulated clodronate, an intracellular toxin taken up by monocyte/macrophages that has been used extensively to study the effects of monocyte depletion in mice. 34,44 To study the contribution of monocytes in HIT, we depleted monocytes with clodronate liposomes in transgenic Fc␥RIIA ϩ /hPF4 ϩ mice. We used flow cytometry to measure the relative number of cells expressing the monocyte differentiation marker CD115 as a proportion of total WBC characterized by expression of CD45.…”

mentioning

confidence: 99%

Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia

Rauova

Hirsch

Greene

et al. 2010

Blood

143

160

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Heparin-induced thrombocytopenia (HIT)is a life-and limb-threatening thrombotic disorder that develops after exposure to heparin, often in the setting of inflammation. We have shown previously that HIT is associated with antibodies to complexes that form between platelet factor 4 and glycosaminoglycan (GAG) side chains on the surface of platelets. However, thrombosis can occur in the absence of thrombocytopenia. We now show that platelet factor 4 binds to monocytes and forms antigenic complexes with their surface GAG side chains more efficiently than on platelets likely due to differences in GAG composition. Binding to monocytes is enhanced when the cells are activated by endotoxin. Monocyte accumulation within developing arteriolar thrombi was visualized by situ microscopy. Monocyte depletion or inactivation in vivo attenuates thrombus formation induced by photochemical injury of the carotid artery in a modified murine model of HIT while paradoxically exacerbating thrombocytopenia. These studies demonstrate a previously unappreciated role for monocytes in the pathogenesis of arterial thrombosis in HIT and suggest that therapies targeting these cells might provide an alternative approach to help limit thrombosis in this and possibly other thrombotic disorders that occur in the setting of inflammation. IntroductionPlatelet factor 4 (PF4) is a cationic chemokine with high affinity for unfractionated heparin (UFH) and other large, negatively charged molecules. 1 PF4 is stored in platelet ␣-granules, released upon activation, when it then binds rapidly to glycosaminoglycan (GAG) side chains expressed on the surface of platelets 2 and other vascular cells, with little remaining free in the circulation. 3 Heparin-induced thrombocytopenia (HIT) is an iatrogenic complication of heparin therapy caused by antibodies that recognize complexes of human (h) PF4 with heparin or other GAGs. 4,5 In solution, formation of antigenic complexes between PF4 and heparin is critically dependent on their molar ratio, with loss of antibody binding when the optimal ratio is disrupted by an excess of either component. 6,7 Antigen formation on the platelet surface also follows a bell-shaped curve as PF4 concentration is increased, with maximal binding of antibody seen at an exogenous PF4 concentration of 50 g/mL. 8 Chondroitin sulfates (CSs) are the predominant GAG side chains expressed on platelets. 9,10 We have shown that the binding of the HIT-like monoclonal antibody KKO 11 to platelets is abrogated by chondroitinase ABC, 8 indicating that HIT antibodies bind to PF4/CS complexes on this cell type. Therapeutic concentrations of UFH disrupt antibody binding in part by eluting PF4 from the platelet surface, which reduces formation of antigenic complexes and the potential for platelet activation 8 through platelet Fc␥RIIA. 12 Thus, variation in the expression of platelet-derived PF4 (or CS) might help to explain why only a small percentage of patients who generate antibodies to PF4/UFH develop HIT. 13 Although it has been generally accepte...

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Liposomes for Specific Depletion of Macrophages from Organs and Tissues

Cited by 327 publications

References 27 publications

Macrophages are required for adult salamander limb regeneration

Macrophages are required for adult salamander limb regeneration

Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia

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