Abstract
We evaluated the use of some neutrophil products, namely; autologous rabbit antimicrobial neutrophil extract (rANE), heterologous porcine antimicrobial neutrophil extract (pANE), neutrophil degranulation products (DGP) and neutrophil microvesicles (MVs) for stimulation of monocyte-derived macrophages (MDMs) to improve healing. Two animal models were evaluated; the rabbit model for autologous osteochondral transplantation (OT) with application of rabbit ANE, DGP or MVs for MDMs stimulation, and the ovine model of the insertion of a Ti implant with the use of porcine ANE, and ovine DGP or MVs for MDMs stimulation. Macrophage activity was assessed on the basis of free radical generation and arginase activity. We estimated that DGP acted in a pro-inflammatory way both on rabbit and ovine MDMs. On the other hand, MVs acted as anti-inflammatory stimulator on MDMs in both experiments. The response to ANE depended on origin of extract (autologous or heterologous). Macrophages from rabbits before and after OT stimulated with autologous extract generated lower amount of NO and superoxide, especially after transplantation. In the ovine model of Ti implant insertion, heterologous ANE evoked increased macrophage pro-inflammatory activity. Our study revealed that these neutrophil products could regulate activity of macrophages, polarizing them into pro-or anti-inflammatory phenotypes that could enhance bone and osteochondral tissue healing.
Highlights
Inflammation as a response of an organism to local injury involves leukocytes migration to damaged sites to fight bacterial infection and to ensure tissue repair
The enzyme activity was compared to maximal release in neutrophil cultures treated with 0.5% Triton X-100 (Sigma-Aldrich) and expressed as percent of activity
We revealed that some neutrophil-derived products, namely; autologous antimicrobial peptides (ANE) and
Summary
Inflammation as a response of an organism to local injury involves leukocytes migration to damaged sites to fight bacterial infection and to ensure tissue repair. Neutrophil granule-derived products appeared to have several roles, from directly killing microorganisms to activating other inflammatory cells, such as monocytes or macrophages [8]. Since neutrophil-derived microvesicles (MVs) exert anti-inflammatory and proresolving properties [18], we evaluated the influence of these structures on macrophage function during repair process. To assess the potential of neutrophil-derived products for modifying of the macrophage response we prepared two animal models; the rabbit model of autologous osteochondral graft and the ovine model of insertion of Ti implant into the tibial growth plate. To assess the potential of neutrophil-derived products for modifying of the macrophage response we prepared two animal models; the rabbit model of autologous oste of 13 ochondral graft and the ovine model of insertion of Ti implant into the tibial growth plate. Model, MDMs were treated in vitro with heterologous porcine neutrophil extract (pANE), ovine DGP or ovine neutrophil MVs
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