The Department of Biomedicine

BBB seminar: Rolf Kåre Reed

β1-integrins in interstitial-capillary interactions: Pathophysiology in inflammation and tumors

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Rolf Kåre Reed
Heart and Circulatory Research Group, Department of Biomedicine, University of Bergen

The lecture will review and update research on the role of connective tissue cells in “active” control of transcapillary exchange via control of the interstitial hydrostatic pressure in a time-course of a few minutes. This control is of particular importance in situations of rapid transcapillary fluid flux causing edema formation where a lowering of interstitial fluid pressure drives the flux from the capillaries into the interstitium. This is contrary to the common notion of the role of the interstitial fluid pressure in control of transcapillary and interstitial volume. The lowering of interstitial pressure has been shown to result from expansion of the interstitial matrix due to its content of glycosaminoglycans following perturbation of the β1-integrins, which are responsible for cell adhesive interactions with the collagen rich microenvironment. The phenomenon of lowering of interstitial pressure occurs in a series of inflammatory reactions and is induced by a series of endogenous inflammatory mediators. Furthermore, other endogenous substances and cytokines will restore the interstitial pressure and thereby the transcapillary fluxes. Also, the increased interstitial pressure in tumors, forming a functional barrier towards transport into the tumor, are influenced by altering the matrix of the tumors within minutes and up to days. The lecture will review the integrins involved in control of interstitial fluid pressure as well as several of the endogenous substances that influence interstitial fluid pressure.