Despite improvements in management of acute allograft rejection and 1 year survival of allografts, many organs succumb sooner or later to chronic allograft rejection/injury. Important contributor to this process is chronic vascular rejection in any organ, and bronchilitis obliterans in transplanted lungs. In the present program project we propose that the abnormal deposits of extracellular matrix seen in bronchioles with obliterative bronchiolitis and arteries with chronic allograft vasculopathy obey to an abnormal humoral and cellular immunity to the generation of excess col(V) al homotrimers in the extracellular matrix. The goal of the Core C, """"""""Pathology Core"""""""" is to provide the histopathology and immunopathology analysis in support of the three proposed projects of the program. Specifically, animal models and human tissues derived from the projects will be analyzed for histomorphologic changes, immunohistochemistry and specialized tissue analysis techniques to characterize extracellular matrix components, and cellular, humoral and soluble mediators of the immune response related to autoimmunity to collagen V in chronic allograft injury. The Core will ensure the appropriate flow of human and animal model tissue between the different institution and laboratories of the program as well as the adequate use of resources pertinent to the Core. The Core has proposed 5 main aims to aid the program projects at different steps, including diagnostic histopathology of biopsies, immunohistochemistry of animal models and human tissue, laser capture microdissection, morphometric analysis and detection of cytokines in human and animal samples. The Core leader. Dr. Jose R. Torrealba, a pathologist specialized in organ transplantation, will provide all the diagnostic histopathology and coordinate the activities of the Core. Numerous manuscripts, including recent publications with the program project Pis, demonstrate the collaboration capabilities and resources of the Core.

Public Health Relevance

The pathology Core will provide histopathology, immunohistochemistry and specialized tissue section analysis for the development and completion of each project of the program project. It will oversee the adequate handling and flow of biological material for tissue analysis between the different institutions and laboratories participating in the program as well as the rational use of resources pertinent to the Core.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Muir, Alison M; Massoudi, Dawiyat; Nguyen, Ngon et al. (2016) BMP1-like proteinases are essential to the structure and wound healing of skin. Matrix Biol 56:114-131
Pandya, Pankita H; Fisher, Amanda J; Mickler, Elizabeth A et al. (2016) Hypoxia-Inducible Factor-1? Regulates CD55 in Airway Epithelium. Am J Respir Cell Mol Biol 55:889-898
Park, Arick C; Huang, Guorui; Jankowska-Gan, Ewa et al. (2016) Mucosal Administration of Collagen V Ameliorates the Atherosclerotic Plaque Burden by Inducing Interleukin 35-dependent Tolerance. J Biol Chem 291:3359-70
Agashe, Vrushali V; Burlingham, William J (2015) Autoimmune Reactivity in Graft Injury: Player or Bystander? Curr Transplant Rep 2:211-221
Wu, Qiang; Gupta, Pawan Kumar; Suzuki, Hidemi et al. (2015) CD4 T Cells but Not Th17 Cells Are Required for Mouse Lung Transplant Obliterative Bronchiolitis. Am J Transplant 15:1793-1804
Park, Arick C; Phillips, Charlotte L; Pfeiffer, Ferris M et al. (2015) Homozygosity and Heterozygosity for Null Col5a2 Alleles Produce Embryonic Lethality and a Novel Classic Ehlers-Danlos Syndrome-Related Phenotype. Am J Pathol 185:2000-11
Pandya, Pankita H; Wilkes, David S (2014) Complement system in lung disease. Am J Respir Cell Mol Biol 51:467-73
Shah, Rupal J; Emtiazjoo, Amir M; Diamond, Joshua M et al. (2014) Plasma complement levels are associated with primary graft dysfunction and mortality after lung transplantation. Am J Respir Crit Care Med 189:1564-7
Sullivan, J A; Jankowska-Gan, E; Shi, L et al. (2014) Differential requirement for P2X7R function in IL-17 dependent vs. IL-17 independent cellular immune responses. Am J Transplant 14:1512-22
Gracon, Adam S A; Wilkes, David S (2014) Lung transplantation: chronic allograft dysfunction and establishing immune tolerance. Hum Immunol 75:887-94

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