Ultrastructural Analysis of Human Epidermal CD44 Reveals Preferential Distribution on Plasma Membrane Domains Facing the Hyaluronan-rich Matrix Pouches

Abstract

We used immunogold staining and stereology to examine the ultrastructural localization and to estimate the relative content of CD44 in different strata and cell types of normal human epidermis. We found that CD44 existed almost exclusively on the plasma membranes; only rare labeling occurred on vesicular structures within the cytoplasm. Quantitation of the immunogold particles indicated that the labeling density of melanocytes corresponded to that of basal keratinocytes, and Langerhans cells displayed a labeling density of ∼10% that of the surrounding spinous cells. Among keratinocyte strata, the highest labeling density occurred on spinous cells, suggesting upregulation of CD44 after detachment from the basement membrane. The plasma membrane distribution of CD44 was compartmentalized, with little signal on cell–cell and cell-substratum contact sites such as desmosomes, the plasma membrane domain facing the basement membrane, and the close apposition of terminally differentiating granular cells. In contrast, CD44 was abundant on plasma membrane domains facing an open intercellular space, rich in hyaluronan. This distribution is in line with a role of CD44 as a hyaluronan receptor, important in the maintenance of the intercellular space for nutritional and cell motility functions in stratified epithelia.