Transcapillary exchange: role and importance of the interstitial fluid pressure and the extracellular matrix

This review will summarize current knowledge on the role of the extracellular matrix (ECM) in general and on the interstitial fluid pressure (Pif) in particular with regard to their importance in transcapillary exchange. The fluid volume in the interstitial space is normally regulated within narrow limits by automatic re-adjustment of the interstitial hydrostatic and colloid osmotic pressures in response to perturbations in capillary filtration and by the lymphatics. Contrary to this commonly accepted view, Pif can become an active force and create a fluid flux across the capillaries in several inflammatory reactions and trauma situations rather than limit the changes occurring. The molecular mechanisms involved in the lowering of Pif include the release of cellular tension exerted on the collagen and microfibril networks in the connective tissue via the collagen-binding β1-integrins, thereby allowing the glycosaminoglycan ground substance, which is normally underhydrated, to expand and take up fluid. Several growth factors and cytokines, including the platelet-derived growth factor BB, are able to reverse a lowering of Pif and restore the normal compaction of the ECM. The magnitude of the lowering of Pif varies with the inflammatory response. In several inflammatory reactions, a lowering of Pif to −5 to −10 mmHg is seen, which will increase capillary filtration by 10–20 times since the normal capillary filtration pressure is usually 0.5–1 mmHg (skin and skeletal muscle). Unless this lowering of Pif is taken into account, the enhanced solute flux resulting from an inflammatory response will be ascribed to an increased capillary permeability.