OBJECTIVE Alternatively activated (M2) macrophages, which are associated with inflammation resolution and tissue repair, are major players in wound healing. Since we showed that ferroportin (Fpn) expression is elevated in M2 macrophages, we investigated the role of macrophage iron in wound repair using a mouse model with macrophage-specific Fpn inactivation. MATERIALS AND METHODS Full-thickness excisional skin wounds on the back of mice lacking Fpn in macrophages (FpnLys/Lys) and Fpnflox/flox littermates was evaluated at 2, 7, 12 days. RESULTS Macroscopical analysis showed that wound closure was delayed in FpnLys/Lys mice compared to littermates at all time points. Histological analysis showed reduced reepithelization, predominance of immature granulation tissue, less fibroblasts and an inflammatory infiltrate characterized by granulocytes. Moreover, in FpnLys/Lys mice, increased iron content was evident in macrophages localized in healing wounds. FACS analysis of mesenchymal (CD 45-) cells showed that at 7 and 12 days after skin excision endothelial (CD31+) cells were less in Fpn Lys/Lys mice than in Fpnflox/flox littermates, whereas no differences were found in leukocytes (CD 45+). Confocal analysis of CD31 and lyve-1 showed a defect of both blood and lymphatic vessel formation, and decreased number of myofibroblasts (α- SMA+) cells at 7 days. Cytokine and growth factors production, evaluated by RT-PCR in 14FACS-sorted macrophages, and by ELISA in wound tissue did not differ significantly in the two mice lines. CONCLUSION Fpn deficiency, with consequent disruption of iron export from macrophages, does not seem to change macrophage polarization but affects wound healing, possibly by impairing growth/differentiation of mesenchymal cells.

Lack of macrophage ferroportin affects wound healing / S. Recalcati, E. Gammella, P. Buratti, M. Locati, G. Cairo. ((Intervento presentato al convegno European Iron Club Meeting tenutosi a Verona nel 2014.

Lack of macrophage ferroportin affects wound healing

S. Recalcati
Primo
;
E. Gammella
Secondo
;
P. Buratti;M. Locati
Penultimo
;
G. Cairo
Ultimo
2014

Abstract

OBJECTIVE Alternatively activated (M2) macrophages, which are associated with inflammation resolution and tissue repair, are major players in wound healing. Since we showed that ferroportin (Fpn) expression is elevated in M2 macrophages, we investigated the role of macrophage iron in wound repair using a mouse model with macrophage-specific Fpn inactivation. MATERIALS AND METHODS Full-thickness excisional skin wounds on the back of mice lacking Fpn in macrophages (FpnLys/Lys) and Fpnflox/flox littermates was evaluated at 2, 7, 12 days. RESULTS Macroscopical analysis showed that wound closure was delayed in FpnLys/Lys mice compared to littermates at all time points. Histological analysis showed reduced reepithelization, predominance of immature granulation tissue, less fibroblasts and an inflammatory infiltrate characterized by granulocytes. Moreover, in FpnLys/Lys mice, increased iron content was evident in macrophages localized in healing wounds. FACS analysis of mesenchymal (CD 45-) cells showed that at 7 and 12 days after skin excision endothelial (CD31+) cells were less in Fpn Lys/Lys mice than in Fpnflox/flox littermates, whereas no differences were found in leukocytes (CD 45+). Confocal analysis of CD31 and lyve-1 showed a defect of both blood and lymphatic vessel formation, and decreased number of myofibroblasts (α- SMA+) cells at 7 days. Cytokine and growth factors production, evaluated by RT-PCR in 14FACS-sorted macrophages, and by ELISA in wound tissue did not differ significantly in the two mice lines. CONCLUSION Fpn deficiency, with consequent disruption of iron export from macrophages, does not seem to change macrophage polarization but affects wound healing, possibly by impairing growth/differentiation of mesenchymal cells.
Settore MED/04 - Patologia Generale
Lack of macrophage ferroportin affects wound healing / S. Recalcati, E. Gammella, P. Buratti, M. Locati, G. Cairo. ((Intervento presentato al convegno European Iron Club Meeting tenutosi a Verona nel 2014.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/470312
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