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Cellular adhesion mechanisms have been recognized as crucial elements regulating the targeting of individual cells to their sites of function. Adhesion determinants direct such critical features as the migration of normal and abnormal skin components in growth and wound healing, the metastatic properties of tumor cells, and the accumulation of leukocytes in the response to infection and in the development of inflammatory diseases. From these observations it is evident that investigation of cell adhesion properties is central to the study of skin pathophysiology. The Leukocyte Migration Core, led by Dr Ulrich von Andrian and Dr. Robert Fuhlbrigge, was developed to provide HSDRC investigators with ready access to expert assistance with the design and execution of high quality assays of human and murine leukocyte adhesion and migration. Analysis of leukocyte migration is complicated by the dynamic nature of the process and the influence of shear flow on leukocytes adhering to post-capillary endothelium. Wall shear stress plays an important role in the regulation and promotion of these interactions. Assay methods that incorporate this dynamic function and address shear-related binding issues have generally only been available in a few highly specialized laboratories around the world. The specialized in vitro and in vivo techniques and extensive experience of the Core Directors have served, and will continue to serve, as the basis for the value of this Core to SDRC investigators. Indeed, the HSDRC Leukocyte Migration Core provides a set of services that is virtually unique in its scope and applications. Heavy use of Core resources over the past five years has reinforced our belief that these technologies are of significant interest to the skin-disease research community and that the expense and complexity of these techniques serves as a barrier to research in these areas. Through the implementation of new technologies, including novel in vitro flow assays and multi-photon confocal intravital microscopy, along with expanded access to more conventional adhesion and migration assay techniques, the Core will continue to provide HSDRC investigators with cutting edge technology for application to their research questions. In addition, mice engineered by Dr. von Andrian to express fluorescent proteins in T cells and/or specific T cell subpopulations, have been produced and characterized and are now available to HSDRC investigators.
The Specific Aims of the Leukocyte Migration Core are as follows:
1. To provide expertise in the planning, execution and analysis of cell adhesion protocols using established standard substrates as well as exploring novel or unknown substrates.
2. To provide instruction and equipment for the execution and analysis of studies employing the parallel plate flow chamber.
3. To provide instruction, equipment and assistance in the execution and analysis of intravital based adhesion studies in ear skin, bone marrow and peripheral lymph node. For comparative analysis, model systems in cremasteric muscle, mesenteric vessels, Peyer’s patches and lamina propria are also available.
4. To provide instruction and assistance in the planning, execution and analysis of skin –specific leukocyte homing in vivo employing defined models of cutaneous inflammation.
Services provided by the Leukocyte Migration Core are divisible into support for in vitro binding studies, in vivo homing model systems and intravital epifluorescence and multi-photon microscopy techniques. Although considerable overlap and collaboration exists, Dr. Fuhlbrigge will continue to provide primary support for in vitro core services at the Harvard Institutes of Medicine and Dr. von Andrian will provide primary support for intravital microscopy core services at the Center for Blood Research. Whole animal in vivo homing studies will be supported in both facilities.
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