Fig. 4

Interaction between the microcirculation and interstitial extracellular matrix during homeostasis and sepsis. In steady state, transcapillary flow is regulated by a solid endothelial barrier and a compacted interstitium with stable, slightly negative pressure (left panel). Fibroblasts apply constant tension to the network of collagen bundles. Fibroblasts’ cytoskeleton is tethered to collagen IV through transmembrane protein ß1 integrin. When inflammation is present (right panel), the binding of collagen bundles by ß1 integrin is inhibited by inflammatory mediators (especially IL-1ß), releasing the physical tension constraining the collagen network, which leads to an abrupt decrease in interstitial pressure [10]. Furthermore, like the glycocalyx, the extracellular matrix is altered by the various proteases released by innate immune cells. The massive increase of transcapillary flow is allowed by the resultant increase in filtration pressure (capillary pressure—interstitial pressure) and by a parallel increase in endothelial permeability due to intercellular adhesion inhibition and glycocalyx shedding