title: Addressing the Inflammatory Response to Clinically Relevant Polymers by Manipulating the Host Response Using ITIM Domain-Containing Receptors.
abstract: Tissue contacting surfaces of medical devices initiate a host inflammatory response, characterized by adsorption of blood proteins and inflammatory cells triggering the release of cytokines, reactive oxygen species (ROS) and reactive nitrogen species (RNS), in an attempt to clear or isolate the foreign object from the body. This normal host response contributes to device-associated pathophysiology and addressing device biocompatibility remains an unmet need. Although widespread attempts have been made to render the device surfaces unreactive, the establishment of a completely bioinert coating has been untenable and demonstrates the need to develop strategies based upon the molecular mechanisms that define the interaction between host cells and synthetic surfaces. In this review, we discuss a family of transmembrane receptors, known as immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors, which show promise as potential targets to address aberrant biocompatibility. These receptors repress the immune response and ensure that the intensity of an immune response is appropriate for the stimuli. Particular emphasis will be placed on the known ITIM-containing receptor, Signal Regulatory Protein Alpha (SIRPhα), and its cognate ligand CD47. In addition, this review will discuss the potential of other ITIM-containing proteins as targets for addressing the aberrant biocompatibility of polymeric biomaterials.
authors.affiliation: Division of Cardiology, Department of Pediatrics, the Children"s Hospital of Philadelphia, Abramson Research Center, Suite 704, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318, USA ; The Perelman School of Medicine, the University of Pennsylvania, Abramson Research Center, Suite 704, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318, USA.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Slee
authors.affiliation: Division of Cardiology, Department of Pediatrics, the Children"s Hospital of Philadelphia, Abramson Research Center, Suite 704, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318, USA ; The Perelman School of Medicine, the University of Pennsylvania, Abramson Research Center, Suite 704, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318, USA.
authors.forename: Abigail J
authors.initials: AJ
authors.lastname: Christian
authors.affiliation: Division of Cardiology, Department of Pediatrics, the Children"s Hospital of Philadelphia, Abramson Research Center, Suite 704, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318, USA ; The Perelman School of Medicine, the University of Pennsylvania, Abramson Research Center, Suite 704, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Levy
authors.affiliation: Division of Cardiology, Department of Pediatrics, the Children"s Hospital of Philadelphia, Abramson Research Center, Suite 704, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318, USA ; The Perelman School of Medicine, the University of Pennsylvania, Abramson Research Center, Suite 704, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318, USA.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Stachelek
keywords: CD200R; CD47; PECAM-1; SIRPα; immunoreceptor tyrosine-based inhibitory motif (ITIM)