CD44 and RHAMM expression patterns in the human developing lung

The hyaluronan (HA) receptors CD44 and RHAMM (CD168) are involved in cellular proliferation, differentiation, and motility. As previously investigated, HA and RHAMM expression in human neonatal lungs correlates to gestational age (GA) and air content.

CD44 immunofluorescence was analyzed in postmortem lung samples from infants (n = 93; 22-41 GA) by digital image analysis together with clinical data, including RHAMM expression, lung air, and HA content by hierarchical clustering.

Five groups were defined according to RHAMM/CD44 expression, GA, and postnatal age (PNA): extremely to very preterm (EVP; 22-31 GA; Groups 1-2), moderately preterm to term (MPT; 31-41 GA; Groups 3-4), and mixed preterm to term (27-40 GA; Group 5). CD44 correlated linearly with RHAMM in MPT (r = 0.600; p < 0.004). In EVP, high CD44 and low RHAMM corresponded with high PNA and lung air content independently of HA and GA (Group 1 vs 2; p < 0.05). In MPT, high and low CD44 corresponded with low and high RHAMM independently of GA, HA, and lung air content (Group 3 vs 4; p < 0.001). No correlation between CD44 and GA/PNA at death was observed.

A linear correlation between CD44 and RHAMM expression occurs during the late saccular phase of lung development at birth, whereas postnatal influences on CD44 and RHAMM expression in extremely to very preterm infants cannot be excluded.

The interplay between CD44 and RHAMM, two receptors of hyaluronic acid, can be dependent on the lung developmental stage at birth. This is the second study that analyzes the distribution pattern of CD44 in the human lung during development and the first study performed with quantitative analysis of CD44 expression together with RHAMM expression in the human lung. Our results suggest a relationship in a subset of infants between CD44 and RHAMM expression, which appears at birth during the late saccular stage but not during the earlier stages of lung development.