Opposite Roles of CCR2 and CX3CR1 Macrophages in Alkali-Induced Corneal Neovascularization

Several chemokines are used for immunotherapy against cancers because they can attract immune cells such as dendritic and cytotoxic T cells to augment immune responses. Radiofrequency ablation (RFA) is used to locally eliminate cancers such as hepatocellular carcinoma (HCC), renal cell carcinoma, and lung cancer. Because HCC often recurs even after an eradicative treatment with RFA, additional immunotherapy is necessary. We treated tumor-bearing mice by administering ECI301, an active variant of CC chemokine ligand 3, after RFA. Mice were injected s.c. with BNL 1ME A.7R.1, a murine hepatoma cell line, in the bilateral flank. After the tumor became palpable, RFA was done on the tumor of one flank with or without ECI301. RFA alone eliminated the treated ipsilateral tumors and retarded the growth of contralateral non-RFA-treated tumors accompanied by massive T-cell infiltration. Injection of ECI301 augmented RFA-induced antitumor effect against non-RFA-treated tumors when administered to wild-type or CCR5-deficient but not CCR1-deficient mice. ECI301 also increased CCR1-expressing CD11c + cells in peripheral blood and RFA-treated tumors after

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“…Clodronate liposome was prepared and systemic depletion of monocytes/macrophages was performed as previously described (20,21). WT mice were i.p.…”

Section: Depletion Of Macrophages/monocytesmentioning

confidence: 99%

Antitumor Effect after Radiofrequency Ablation of Murine Hepatoma Is Augmented by an Active Variant of CC Chemokine Ligand 3/Macrophage Inflammatory Protein-1α

et al. 2010

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“…In contrast, CX3CR1-deficient animals subjected to corneal injuries exhibited increased vascularization, along with decreased local production of antiangiogenic mediators thrombospondin 1 and 2 and their activator ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin motif-1). 56 It is possible that the role of wound macrophages in angiogenesis varies with injury site. It is more likely that the cells provide proangiogenic and antiangiogenic signals in wounds and that the balance of these signals regulates the early angiogenic response during granulation tissue formation and its resolution as the scar matures.…”

Section: Wound Macrophages and Neovascularizationmentioning

confidence: 99%

Wound Macrophages as Key Regulators of Repair

Brancato

Albina

2011

The American Journal of Pathology

459

389

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Recent results call for the reexamination of the phenotype of wound macrophages and their role in tissue repair. These results include the characterization of distinct circulating monocyte populations with temporally restricted capacities to migrate into wounds and the observation that the phenotype of macrophages isolated from murine wounds partially reflects those of their precursor monocytes, changes with time, and does not conform to current macrophage classifications. Moreover, findings in genetically modified mice lacking macrophages have confirmed that these cells are essential to normal wound healing because their depletion results in retarded and abnormal repair. This mini-review focuses on current knowledge of the phenotype of wound macrophages, their origin and fate, and the specific macrophage functions that underlie their reparative role in injured tissues, including the regulation of the cellular infiltration of the wound and the production of transforming growth factor-␤ and vascular endothelial growth factor. The resolution of injury through replacement by scar has been preserved in evolution and applies to virtually all soft tissues in mammals. A healed wound is the result of the activities of cells that constitute what can be conceptually described as a wound organ. This transient neoorgan is assembled at the time and site of injury and disassembled once repair is complete, leaving in place a scar as evidence of the repair process. The parenchyma of the wound organ is composed of a temporally changing assembly of inflammatory cells, neovessels, fibroblasts and myofibroblasts, regenerating nerves, and other cells specific to the site of the injury (eg, keratinocytes, osteocytes, and hepatocytes).Two recent developments led to this review of wound macrophages. First, studies in both humans and rodents have demonstrated the existence of diverse subpopulations of circulating monocytes with, at least in mice, distinct and time-restricted abilities to migrate into wounds and other sites of tissue injury (Figure 1). These immediate precursors of wound macrophages are required for repair by scarring in organs as diverse as skin, heart, liver, and kidney. Second, the concept that macrophages involved in tissue repair express the alternatively activated phenotype first proposed by Gordon 1 has been retained in the literature.2 Results from studies of macrophages isolated from wounds, however, contest this paradigm by demonstrating that they are not alternatively activated. Wound macrophages exhibit phenotypes that partially reflect those of their monocyte precursors, change with time, and fail to be adequately described by macrophage classifications based on activation profiles or functional capacity (Figure 2). 3This review addresses the origin and fate of wound macrophages, their regulatory interactions with other cellular populations in the wound, and the roles of macrophagederived transforming growth factor-␤ (TGF-␤) and vascular endothelial growth factor (VEGF) in the regulation of wound fibrosis an...

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“…These results provide insight into the mechanism triggering CoNV and can be integrated with data that have indicated macrophage (10,20,21,41) and neutrophil (11,12) involvement in amplifying this response. One interpretation of the current data is that the mechanisms driving debridement-induced CoNV differ from other injuries, such as alkali burn or suture.…”

Section: Discussionmentioning

confidence: 94%

Pharmacologic Uncoupling of Angiogenesis and Inflammation during Initiation of Pathological Corneal Neovascularization

Sivak

Ostriker

Woolfenden³

et al. 2011

Journal of Biological Chemistry

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Opposite Roles of CCR2 and CX3CR1 Macrophages in Alkali-Induced Corneal Neovascularization

Abstract: Because CCR2- and CX3CR1-expressing macrophages exhibit opposite activities in angiogenesis, depletion of macrophages as a whole may not have apparent effects on alkali-induced corneal neovascularization.

Cited by 40 publications

References 33 publications

Antitumor Effect after Radiofrequency Ablation of Murine Hepatoma Is Augmented by an Active Variant of CC Chemokine Ligand 3/Macrophage Inflammatory Protein-1α

Antitumor Effect after Radiofrequency Ablation of Murine Hepatoma Is Augmented by an Active Variant of CC Chemokine Ligand 3/Macrophage Inflammatory Protein-1α

Wound Macrophages as Key Regulators of Repair

Pharmacologic Uncoupling of Angiogenesis and Inflammation during Initiation of Pathological Corneal Neovascularization

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