Aruffo et al. (1990) demonstrated that CD44 is the main cell surface receptor for hyaluronate. Hyaluronan or hyaluronic acid (HA) is a high molecular weight unbranched polysaccharide synthesized by a wide variety of organisms from bacteria to mammals, and is a constituent of the extracellular matrix.

Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Ashkar S et al. Cell-mediated (type-1) immunity is necessary for immune protection against most intracellular pathogens and, when excessive, can mediate organ-specific autoimmune destruction. ... A phosphorylation-dependent interaction between the amino-terminal portion of Eta-1 and its integrin receptor stimulated IL-12 expression, whereas a phosphorylation-independent interaction with CD44 inhibited IL-10 expression. These findings identify Eta-1 as a key cytokine that sets the stage for efficient type-1 immune responses through differential regulation of macrophage IL-12 and IL-10 cytokine expression.

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Phosphorylation-dependent interaction of osteopontin with its receptors regulates macrophage migration and activation. Weber GF et al. Neutrophil-independent macrophage responses are a prominent part of delayed-type immune and healing processes and depend on T cell-secreted cytokines. An important mediator in this setting is the phosphoprotein osteopontin, whose secretion by activated T cells confers resistance to infection by several intracellular pathogens through recruitment and activation of macrophages. ... These data, taken as a whole, indicate that the activities of distinct osteopontin domains are required to coordinate macrophage migration and activation and may bear on incompletely understood mechanisms of delayed-type hypersensitivity, wound healing, and granulomatous disease.

EGF receptor modifies cellular responses to hyaluronan in glioblastoma cell lines. Tsatas D et al. Cell contact with the extracellular matrix component, hyaluronan, plays a pivotal role in glioma cell invasion and proliferation. Although it is well established that glioma cells can bind hyaluronan to their surface via the expression of CD44, the cellular responses following ligand-receptor interaction remain poorly understood. ... Here we present evidence that CD44 co-immunoprecipitates with EGFR and ErbB2 in the glioma cell lines U87MG and SMA560. ... These results indicate a novel functional relationship between CD44 and EGFR in glioma cell lines. ... These findings provide new insights into the mode by which hyaluronan regulates the malignant phenotype and also suggest a role for EGFR-CD44 interactions in glial tumorigenesis.

CD44 is a major E-selectin ligand on human hematopoietic progenitor cells. J Cell Biol. 2001