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Hyaluronan as a space-filling material and organizer of an extensive extracellular matrix is a straightforward concept in mesenchymal/mesenchyme-derived tissues such as the dermis and cartilage. The functions of hyaluronan are less obvious in epithelial tissues, in which the cells are closely spaced and appear to have very little extracellular space (Fig. 1).

 

Indeed, a high concentration of hyaluronan would likely swell the extracellular spaces, possibly disrupting the cohesion between epithelial cells and compromising the epithelial permeability barriers. In view of this, it is not surprising that most simple epithelia, such as those in the normal gastrointestinal2, respiratory, and reproductive tracts, express little or no hyaluronan.

 

 On the other hand, the vital parts of stratified epithelia in skin and of the oral, esophageal, and vaginal mucosa all exhibit an intense pericellular signal when stained with a hyaluronan-specific probe prepared from cartilage aggrecan and link protein (see Hardingham, in this series). In addition, epidermis can now be separated from dermis by chelating divalent cations with solutions of EDTA, allowing the epidermal hyaluronan content to be measured accurately.

 

Although the amount appears relatively low (0.**0.2 microg/mg dry weight), its restriction to the small extracellular space of this tissue indicates that its concentration around the cells may be as high as 2.5 mg/ml, depending on the accuracy of current estimates of the extracellular volume