Intracorporally implanted materials, such as medical devices, will provoke the body to initiate an inflammatory reaction. This inflammatory reaction to implanted materials is known as the foreign body reaction (FBR) and is characterized by 3 distinct phases: onset, progression, and resolution. The FBR proceeds in the creation of a dynamic microenvironment that is spatially well organized. The progression of the FBR is regulated by soluble mediators, such as cytokines, chemokines, and matrix metalloproteinases (MMPs), which are produced locally by tissue cells and infiltrated inflammatory cells. These soluble mediators orchestrate the cascade of cellular processes in the microenvironment that accompanies the FBR, consisting of cellular activation, angiogenesis, extravasation, migration, phagocytosis, and, finally, fibrosis. The nature of the FBR requires that the soluble mediators act in a spatial and temporally regulated manner as well. This regulation is well known for several inflammatory processes, but scarce knowledge exists about the intricate relationship between the FBR and the expression of soluble mediators. This review discusses the key processes during the initiation, progression, and resolution phase, with emphasis on the role of soluble mediators. Besides other sites of implantation, we focus on the subcutaneous implantation model.

The epithelial cell adhesion molecule (EpCAM , CD326) is a glycoprotein of ϳ40 kd that was originally identified as a marker for carcinoma, attributable to its high expression on rapidly proliferating tumors of epithelial origin. Normal epithelia express EpCAM at a variable but generally lower level than carcinoma cells. In early studies, EpCAM was proposed to be a cell-cell adhesion molecule. However, recent insights revealed a more versatile role for EpCAM that is not limited only to cell adhesion but includes diverse processes such as signaling, cell migration, proliferation, and differentiation. Cell surface expression of EpCAM may actually prevent cell-cell adhesion. Here, we provide a comprehensive review of the current knowledge on EpCAM biology in relation to other cell adhesion molecules. We discuss the implications of the newly identified functions of EpCAM in view of its prognostic relevance in carcinoma , inflammatory pathophysiology , and tissue development and regeneration as well as its role in normal epithelial homeostasis.

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