Disease relevance of CD44

• Therefore, CD44 targeting with specific monoclonal antibodies (mAbs) should be useful for the inhibition of collagen-induced arthritis (CIA) as well as other autoimmune diseases that are dependent on inflammatory cells [1].
• These data show that mAbs against several adhesion molecules are able to block selectively distinct aspects of immune reactions, and that CD44 and alpha 4-integrins could be promising targets for an immunotherapy of rheumatoid arthritis with receptor-interfering agents [2].

High impact information on CD44

• CD44 is a broadly distributed polymorphic glycoprotein that serves as the principal cell-surface receptor for hyaluronate [3].
• Selective suppression of CD44 in keratinocytes of mice bearing an antisense CD44 transgene driven by a tissue-specific promoter disrupts hyaluronate metabolism in the skin and impairs keratinocyte proliferation [3].
• Although CD44-mediated cell interaction with hyaluronate has been implicated in a variety of physiologic events, including cell-cell and cell-substrate adhesion, cell migration, proliferation, and activation, as well as hyaluronate uptake and degradation, the biologic role of CD44 in vivo in various tissues remains to be determined [3].
• A CD44-like endothelial cell transmembrane glycoprotein (GP116) interacts with extracellular matrix and ankyrin [4].
• The accumulation of intracellular ITEGE and DIPEN neoepitopes in bovine articular chondrocytes is mediated by CD44 internalization of hyaluronan [5].

Biological context of CD44

• In contrast to proliferation, activation-induced apoptosis of CD4(+) cells resulted in a significant down regulation of CD44 expression [6].
• The predicted amino acid sequence of bovine CD44 has an overall high similarity with that of human and mouse CD44, 79.5 and 73.2%, respectively [7].
• Hyaluronan is involved in fundamental reproductive events such as sperm storage in the female reproductive tract, fertilization, and early embryo development, these functions are presumably mediated by its major cell surface receptor, CD44 [8].
• Our observations indicate that two major functions of CD44 in skin are the regulation of keratinocyte proliferation in response to extracellular stimuli and the maintenance of local hyaluronate homeostasis [3].
• Together, these findings strongly suggest that phosphorylation of the transmembrane glycoprotein GP116 (a CD44-like molecule) by protein kinase C is required for effective GP116-ankyrin interaction during endothelial cell adhesion events [4].

Anatomical context of CD44

• Expression of L-Selectin (CD62L), CD44, and CD25 on activated bovine T cells [6].
• Lymphocytes obtained from lungs of M. bovis-infected cattle also had reduced expression of CD44 compared to lymphocytes from lungs of noninfected cattle [6].
• CD44 is a cell-surface glycoprotein involved in leukocyte adherence, T-cell activation and lymphocyte homing [7].
• Detection of the hyaluronan receptor CD44 in the bovine oviductal epithelium [8].
• While positive immunolabelling for CD44 was found on the ad-luminal surface and supra-nuclear region of epithelial cells in all tubal segments investigated, in the UTJ, there were epithelial cells in which the entire cytoplasm positively stained [8].

Associations of CD44 with chemical compounds

• We used complementary biochemical and immunological techniques to establish that an endothelial cell transmembrane glycoprotein, GP116, is a CD44-like molecule and binds directly both to extracellular matrix components (e.g., hyaluronic acid) and to ankyrin [4].
• METHODS: Binding and internalization of a variety of fluorescein isothiocyanate (FITC)- or biotin-labeled HA/proteoglycan probes were investigated on normal bovine articular cartilage chondrocytes, bovine articular chondrocytes transfected with a dominant-negative construct of CD44, or COS-7 cells transfected with wild-type CD44 [9].
• As for HA the luminal epithelium was devoid of CD44 [10].
• We conclude that incubation with oleic acid increases expression of CD44 and increases capping of both CD44 and CD45 [11].
• Incubation with oleic acid, but not stearic acid or BSA alone, was associated with an increase in FI of CD44 [11].

Other interactions of CD44

• In bovine COCs, the transcriptional up-regulation of both HAS2 and the receptor CD44 appear to be important prerequisites for initiating HA-mediated effects during final oocyte development and sperm-egg interaction [12].
• In both assays, treatment of cells with reagents that block CD44 (hyaluronan oligosaccharides or monoclonal Ab IM7) or annexin V (polyclonal Ab #8958) had no detectable effect on adhesion [13].
• In this study, the effects of fragmentation of the glycosoaminoglycans of the cell-associated matrix by hyaluronidase (HAase) on the expression of CD44 receptor and matrix metalloproteinase (MMP) mRNAs in cultured articular chondrocytes were examined [14].

Analytical, diagnostic and therapeutic context of CD44

• Presence of CD44 was detected by Western blotting in the tubal epithelium as a single band at 200 kDa [8].
• Localization of CD44 and HA were done by immunohistochemistry and biotinylated HA-binding protein, respectively [12].
• CD44 involvement in experimental collagen-induced arthritis (CIA) [1].
• Cytoskeletal disruption did not reduce CD44 expression, as monitored by flow cytometry, but detergent extraction of CD44 was enhanced and hyaluronan binding was decreased [15].
• Introducing quantitative real-time RT-PCR, a remarkable cyclic change of CD44 occurred [10].

References