ABSTRACT
Cell interactions with constituents of the extracellular matrix (ECM) are fundamental to a variety of processes ranging from embryonic development to host responses to infection and injury, to tumor growth and metastasis. While much attention has been given to cell interactions with protein members of the ECM, there is increasing recognition that receptor-mediated cell interactions with hyaluronan (hyaluronic acid; HA), a glycosaminoglycan constituent of the ECM, may also be of considerable importance. Specifically, a growing body of literature has provided compelling evidence for the role of HA and its major receptors (CD44 and RHAMM) in cell proliferative and motility responses required for wound healing, inflammatory cell recruitment and activation, and angiogenesis. This is particularly relevant to the lung, where HA has been implicated in lung development and may be important in inflammatory responses that contribute to the pathogenesis of acute lung injury, neonatal lung diseases, airway mucosal defense, and even emphysema. As our understanding of the role of HA and its receptors in lung health progresses, new and potentially very exciting approaches to treating important human lung diseases, based on inhibition of HA-dependent interactions, may emerge.
