INNATE IMMUNITY, C-REACTIVE PROTEIN AND WOUND HEALING

急性期宿主防御反应（APR）是先天（非特异性，天然）免疫的一种生存机制，由身体触发，作为对组织完整性的任何轻微或重大威胁的立即反应。组织的任何损伤或破坏，例如在伤口中发生的，都会损害先天免疫的两个重要功能，1。作为物质进入和流动的障碍，以及2.）作为一种基质，宿主防御和组织修复的反应在其中发出信号并协调。APR的关键蛋白是C反应蛋白（GRP）。最近，CRP的构象类似物（即mCRP）已被研究为在健康纤维结缔组织中天然存在的自聚合蛋白质。静脉注射mCRP在各种癌症和感染性疾病的动物模型中具有治疗活性。本研究将在正常和受损伤口愈合模型中检查局部用重组mCRP（rmCRP）治疗的部分厚度和全厚度伤口的组织再生和修复的速率和程度。这项工作的目标是确定将先天免疫蛋白和APR引入损伤组织的安全性和有效性，并确定rmCRP用于伤口愈合适应症的商业潜力。拟议的商业应用：mCRP作为CRP的天然类似物的发现可能有一天被认为是利用天然（先天）免疫系统获得治疗优势的关键桥梁。通过在组织中沉积，mCRP可用作增加屏障（针对感染、转移和炎症）的主要疗法，以及用作放大急性期反应的有益反应的辅助疗法。基本上所有组织虚弱的患者都可以作为治疗的目标。由于mCRP是“原始”宿主防御系统的一个组成部分，它可能对愈合机制受损的免疫抑制个体特别有效。适合商业化的mCRP的重组形式已经大量可用。

The acute phase host defense response (APR) is a survival mechanism of innate (non-specific, natural) immunity, triggered by the body as an immediate response to any minor or major threat to tissue integrity. Any damage or breach of tissues, such as occurs in wounds, compromises two important functions of innate immunity, 1.) as a barrier to the entry and movement of substances, and 2.) as a matrix within which reactions of host defenses and tissue repair are signaled and coordinated. A key protein of the APR is C-reactive protein (GRP). Recently, a conformational analog of CRP (i.e. mCRP) has been studied as a self- polymerizing protein naturally found in healthy, fibrous connective tissues. Intravenous mCRP has therapeutic activity in various animal models of cancer and infectious disease. This study will examine the rate and extent of tissue regeneration and repair of both partial thickness and full thickness wounds topically treated with recombinant mCRP (rmCRP), in both normal and impaired wound healing models. The goal of this work is to establish the safety and effectiveness of introducing a protein of innate immunity and the APR into injured tissues, and to establish the commercial potential of rmCRP for wound healing indications. PROPOSED COMMERCIAL APPLICATIONS: The discovery of mCRP as a naturally-occurring analog of CRP may one day be considered a key bridge to exploiting the natural (innate) immune system to therapeutic advantage. By depositing in tissues, mCRP may be used as a primary therapy to increase barriers (against infections, metastases, and inflammation), and as an adjunctive therapy to amplify beneficial reactions of the acute phase response. Essentially all patients with weakened tissues could be targeted for treatment. Because mCRP is a component of the "primitive" host defense system, it may be particularly effective in immunosuppressed individuals with impaired healing mechanisms. A recombinant form of mCRP suitable for commercialization is already available in large quantities.