Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/20955
Title: Modifiers of inflammatory angiogenesis in a murine model
Authors: GONG YUE
Keywords: neutrophils. lymphocytes. angiogenesis. wound healing. VEGF
Issue Date: 29-Mar-2010
Source: GONG YUE (2010-03-29). Modifiers of inflammatory angiogenesis in a murine model. ScholarBank@NUS Repository.
Abstract: Wound healing is a body?s response to injury, in which angiogenesis play a critical part. Immune cells play a role in both angiogenesis and wound healing. Understanding the mechanisms of wound healing, angiogenesis in the context of the immune response will help lay the foundation for better treatment of pathologies related to aberrant angiogenesis and wound healing. The roles of neutrophils in angiogenesis have been implicated by previous studies. However, no direct in vivo evidence relates the neutrophil to natural inflammatory angiogenesis. Moreover, there are controversial results on the role of neutrophils in wound healing. Similarly, although lymphocytes have been shown to produce angiogeneic factors in pathological conditions, the role of lymphocytes in natural inflammatory angiogenesis is still unclear. Lymphocytes play an important part in skin wound healing, but the mechanism need further exploration. In the present study, we investigated the role of neutrophils in inflammatory angiogenesis and wound healing in the corneal and skin injury model by depleting neutrophil using RB6-8C5, a neutrophil-depleting antibody. We also investigated the role of lymphocytes in inflammatory angiogenesis and wound healing by establishing the corneal and skin injury model on Rag1 knock-out mice and the control mice. Angiogenesis, inflammatory cell infiltration, protein levels of vascular endothelial growth factor (VEGF) macrophage inflammatory protein-1alpha (MIP-1a), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor alpha (TNF-a) were investigated in the injured cornea and skin of control and RB6-8C5-treated mice. An in vitro model of neutrophil activation was also used to examine the ability of neutrophils to produce and release VEGF, MIP-1a, and MIP-2. We found that enhanced protein levels of VEGF, MIP-1a, and MIP-2 correlated with the degree of neutrophil infiltration in the corneal and skin injury model. Neutrophil depletion significantly inhibited angiogenesis and reduced the protein levels of VEGF, MIP-1a, and MIP-2 in the injured cornea and skin. Upon stimulation, isolated neutrophils released VEGF from preformed stores and MIP-1a and MIP-2 by de novo synthesis. The skin injury model was also used to study the role of neutrophils in skin wound healing. We observed the wound healing rate, protein levels of monocyte chemotactic protein-1 (MCP-1), and transforming growth factor beta-1(TGF-?1) and scar formation in the skin wound healing model. We found that neutrophil depletion severely impaired wound healing rate, and reduced the protein levels of TGF-?1. In the present study we found that there was no difference in angiogenesis in the corneal and skin injury model between Rag1KO and control mice. This finding indicates that lymphocytes may not play a role in the inflammatory angiogenesis. However, the skin wound healing was delayed in the Rag1KO mice compared with control mice. There were no differences in neutrophil and monocyte infiltration, angiogenesis, and the protein levels of VEGF, MIP-1a, MCP-1 and TNF-a between the Rag1KO and control mice. In the Rag1KO mice, the protein levels of MIP-2 and TGF-?1 was decreased. In conclusion, neutrophils play an important role in the natural inflammatory angiogenesis most likely by releasing proangiogenic factors such as VEGF. Neutrophils play an important role in wound healing by inducing angiogenesis and the upregulation of TGF-?1. Lymphocytes may not play a significant role in inflammatory angiogenesis. They play an important role in skin wound healing, unrelated to angiogenesis.
URI: http://scholarbank.nus.edu.sg/handle/10635/20955
Appears in Collections:Ph.D Theses (Open)

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