A MODEL FOR THE ROLE OF HYALURONIC-ACID AND FIBRIN IN THE EARLY EVENTS DURING THE INFLAMMATORY RESPONSE AND WOUND-HEALING
A MODEL FOR THE ROLE OF HYALURONIC-ACID AND FIBRIN IN THE EARLY EVENTS DURING THE INFLAMMATORY RESPONSE AND WOUND-HEALING
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DOI：
10.1016/s0022-5193(86)80076-5
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发表时间：
1986-03-21
影响因子：
2
通讯作者：
LEBOEUF, RD
中科院分区：
文献类型：
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作者：
WEIGEL, PH;FULLER, GM;LEBOEUF, RD
一个模型概述了在伤口愈合过程的早期阶段发生的分子和细胞事件。潜在的主题是，在纤维蛋白（主要凝块蛋白）和透明质酸（HA）（伤口细胞外基质的成分）之间存在特异性结合相互作用。这种结合相互作用，也可以通过其他交联组分稳定，提供了组织三维HA基质的驱动力，所述HA基质附着于初始纤维蛋白基质并与初始纤维蛋白基质交叉。HA-纤维蛋白基质在随后的组织重建过程中起主要作用。我们认为，HA和纤维蛋白在伤口愈合过程中的不同时间具有结构和调节功能。血液和初始凝块中HA的浓度非常低。这与HA和纤维蛋白（原）之间的拟定相互作用一致，可能干扰纤维蛋白原活化或纤维蛋白组装和交联。我们提出，在凝血反应期间产生激活剂（例如，源自血浆前体、血小板或周围细胞），然后刺激一种或多种血细胞类型合成HA并将其分泌到凝块的纤维蛋白基质中。我们预测HA通过调节纤维蛋白的降解来控制基质的稳定性。新的HA-纤维蛋白基质增加或稳定凝块的体积和孔隙度，然后用作物理支持物，即捕获在凝块中的细胞或从伤口外周边缘浸润的细胞可以通过其迁移的支架。HA-纤维蛋白基质还积极刺激或诱导细胞运动性，并激活和调节血细胞的许多功能，这些功能参与炎症反应，包括吞噬作用和趋化性。然后，随着细胞继续迁移到伤口中，第二HA-纤维蛋白基质本身被修饰，分泌透明质酸酶和纤溶酶原激活剂以降解HA和纤维蛋白。同时，这些细胞分泌胶原蛋白和糖胺聚糖以形成更分化的基质。衍生自纤维蛋白和HA的降解产物又是重要的调节分子，其控制参与愈合伤口中的炎症反应和新血管形成的细胞功能。该模型产生了一些可测试的实验预测。
A model is presented outlining the molecular and cellular events that occur during the early stages of the wound healing process. The underlying theme is that there is a specific binding interaction between fibrin, the major clot protein, and hyaluronic acid (HA), a constituent of the wound extracellular matrix. This binding interaction, which could also be stabilized by other cross-linking components, provides the driving force to organize a three-dimensional HA matrix attached to and interdigitated with the initial fibrin matrix. The HA-fibrin matrix plays a major role in the subsequent tissue reconstruction processes. We suggest that HA and fibrin have both structural and regulatory functions at different times during the wound healing process. The concentration of HA in blood and in the initial clot is very low. This is consistent with the proposed interaction between HA and fibrin(ogen), which could interfere with either fibrinogen activation or fibrin assembly and cross-linking. We propose that an activator (e.g. derived from a plasma precursor, platelets or surrounding cells) is produced during the clotting reaction and then stimulates one or more blood cell types to synthesize and secrete HA into the fibrin matrix of the clot. We predict that HA controls the stability of the matrix by regulating the degradation of fibrin. The new HA-fibrin matrix increases or stabilizes the volume and porosity of the clot and then serves as a physical support, a scaffold through which cells trapped in the clot or cells infiltrating from the peripheral edge of the wound can migrate. The HA-fibrin matrix also actively stimulates or induces cell motility and activates and regulates many functions of blood cells, which are involved in the inflammatory response, including phagocytosis and chemotaxis. The secondary HA-fibrin matrix itself is then modified as cells continue to migrate into the wound, secreting hyaluronidase and plasminogen activator to degrade the HA and fibrin. At the same time these cells secrete collagen and glycosaminoglycans to make a more differentiated matrix. The degradation products derived from both fibrin and HA are, in turn, important regulatory molecules which control cellular functions involved in the inflammatory response and new blood vessel formation in the healing wound. The proposed model generates a number of testable experimental predictions.