Disease relevance of Cd44

• CD44-deficient lymphocytes from animals with chronic arthritis, but not from those with transient peritonitis, expressed markedly reduced levels of the lymph node homing receptor, L-selectin [1].
• Flow cytometric analysis of lymphocyte populations from lymphomas in six recipients revealed that, while all lymphomas expressed phenotypic markers of immature cortical thymocytes, i.e., Thy-1, Pgp-1, Jlld, and CD5, they were not uniform with regard to other T-cell markers, notably CD4 and CD8 [2].
• In contrast, H-2, Pgp-1 and T-200 gps were excluded from the budding of both virus particles [3].
• Using the indirect immunoelectron microscopy technique, it was investigated whether during assembly of murine leukaemia virus (MuLV) and vesicular stomatitis virus (VSV), the glycoproteins (gp) Thy-1, H-2, Pgp-1 and T-200 present on the surface of BW5147 and BuEL4 leukaemia cell lines were incorporated into the virus envelopes [3].
• Direct demonstration of the infiltration of murine central nervous system by Pgp-1/CD44high CD45RB(low) CD4+ T cells that induce experimental allergic encephalomyelitis [4].

High impact information on Cd44

• In the transitional B cells, early markers of differentiation such as Pgp1 (CD44) and ThB reach the highest level of expression, while the expression of CD23 and mIgD, late markers of differentiation, and expression of class II MHC, progressively increases [5].
• Thy-1, Pgp-1 and CD45R expression on both normal and induced gamma/delta T cells was consistent with an activation phenotype [6].
• Also in male but not female alpha/beta TCR transgenic mice, the CD8+ cells with the transgenic TCR bear the Pgp1 marker characteristic of mature T cells activated by antigen [7].
• Previous studies in humans and mice have implicated Pgp-1/CD44-related glycoproteins in the migration of peripheral lymphoid cells, as well as interactions of cells with the extracellular matrix [8].
• A cell adhesion model was previously used to select a series of monoclonal antibodies (mAbs), which were subsequently found to recognize CD44/Pgp-1 [9].

Chemical compound and disease context of Cd44

• Specific selection of host cell glycoproteins during assembly of murine leukaemia virus and vesicular stomatitis virus: presence of Thy-1 glycoprotein and absence of H-2, Pgp-1 and T-200 glycoproteins on the envelopes of these virus particles [3].
• Two Pgp-1-positive thymomas that did not bind hyaluronic acid were induced by phorbol ester to bind hyaluronic acid with the same specificity as other hyaluronic acid-binding lines [10].

Biological context of Cd44

• Allografting induces the down-regulation of gp90 and up-regulation of Pgp-1 on a subset of cells, resulting in the appearance of CD8+gp90-Pgp-1hi (Pop. 3) cells [11].
• However, cells from WT and CD44-deficient mice with collagen-induced arthritis showed distinct migration kinetics upon transfer to arthritic recipients [1].
• To investigate whether signals activated by adhesion receptors have a similar activity, we analyzed the effect of CD44 (Pgp-1) adhesion molecule receptor stimulation on T-cell apoptosis induced by three stimuli (anti-CD3 MoAbs, dexamethasone [DEX] treatment, and exposure to ultraviolet irradiation [UV]) on a 3DO T-cell line [12].
• The identification of a new alternative exon with highly restricted tissue expression in transcripts encoding the mouse Pgp-1 (CD44) homing receptor. Comparison of all 10 variable exons between mouse, human, and rat [13].
• Portions of the deduced amino acid sequence were identical to those obtained by amino acid sequence analysis from the purified glycoprotein, confirming that the cDNA encodes Pgp-1 [14].

Anatomical context of Cd44

• The gene has been provisionally designated Pgp-1 for phagocyte glycoprotein 1 [15].
• We now report that, late after rejection of minor histocompatibility Ag-disparate skin grafts, the majority of memory CD8 T cells express both L-selectin and Pgp-1 and thus would be expected to migrate via the classical route of recirculation through LN [16].
• While lymphocytes from CD44(-/-) mice preferentially homed to lymph nodes, their entry into the inflamed synovial joints was delayed as compared with WT cells [1].
• These results suggest that CD44 plays opposite roles in the regulation of leukocyte traffic to inflammatory sites versus the lymph nodes [1].
• CD44 has been implicated in hyaluronan (HA)-dependent primary adhesion between leukocytes and endothelium [1].

Associations of Cd44 with chemical compounds

• The predicted structure of Pgp-1 includes an NH2-terminal extracellular domain (residues 14-265), a transmembrane domain (residues 266-286), and a cytoplasmic tail (residues 287-358) [14].
• In contrast, C71/26 and other MoAbs against Pgp-1 inhibited platelet-dependent cytotoxicity of antibody-coated sheep erythrocytes in the presence of C5-deficient mouse plasma whereas M1/70 against CR3 showed no effect [17].
• We show that the ionomycin-resistant cell population is enriched for cells that express high levels of Pgp-1 (CD44), and low levels of CD45RB, and thus appears to consist largely of memory T cells [18].
• A high percentage of cells recovered after 7 to 14 days from IL-7-supplemented LSC resembled the earliest detectable fetal thymocytes with regard to cell surface markers: they expressed Pgp-1, lacked CD4, CD8, and CD3 and many expressed the IL-2R [19].
• We used the monoclonal mouse anti-human phagocytic glycoprotein-1 CD44 (clone DF 1485), on formalin-fixed, paraffin-embedded tissue [20].

Regulatory relationships of Cd44

• CD44 (Pgp-1) inhibits CD3 and dexamethasone-induced apoptosis [12].

Other interactions of Cd44

• The strong expression of CD44 antigen on abnormal double negative T cells of lymph nodes was characteristic in MRL-lpr mice [21].
• Mac-1 and B220 were absent from all fibroblastic cells studied, whereas the Forsmann and Pgp-1 antigens were always present [22].
• Following activation Pgp-1, the interleukin-2 (IL-2) receptor (as detected by the monoclonal antibody 7D4) and the peanut agglutinin (PNA) receptor were gained by a proportion of cells, MEL-14 was lost by a proportion of cells, and no change was observed in the expression of heat stable antigen [23].
• During T cell development, however, changes in expression of Pgp-1, MEL-14, the IL-2 receptor and the PNA receptor may be associated with activation, rather than differentiation per se [23].
• Using CcS-19, one of the highly susceptible RC strains, we mapped a novel colon tumor susceptibility gene, Scc-1, different from the oncogenes and tumor-suppressor genes known to be involved in colon tumorigenesis, in the vicinity of CD44 (Ly-24, Pgp-1) on chromosome 2 [24].

Analytical, diagnostic and therapeutic context of Cd44

• In Northern blot analysis, only cells expressing Pgp-1 contained mRNA species that hybridized with this Pgp-1 cDNA [14].
• Molecular cloning and expression of Pgp-1. The mouse homolog of the human H-CAM (Hermes) lymphocyte homing receptor [25].
• Platelets and monocyte/macrophage cells from either peripheral blood or from the peritoneal cavity showed homogeneous binding of Pgp-1 antibody to greater than 97% of cells by flow cytometry [17].
• The presence of the Pgp-1 glycoprotein on mouse platelets is demonstrated by antibody-binding techniques, by immunoprecipitation, and by transblotting using the monoclonal antibody (MoAb) C71/26 against Pgp-1 [17].
• Immunoblotting showed Pgp-1 expression on platelets to be quantitatively similar to its presence on macrophages and resolved platelet Pgp-1 into two bands of mol wt 87,000 and 97,000 whereas Pgp-1 on parasite-elicited peritoneal macrophages showed 82,000 and 87,000 mol wt species [17].

References