Disease relevance of SPN

• CD7 and CD43 colocalized in small patches away from the membrane blebs, which excluded externalized phosphatidylserine [1].
• We demonstrate here that CD43 cross-linking potentiates HIV-1 promoter-driven activity and virus production that is seen following the engagement of the T-cell receptor (TCR).CD3 complex [2].
• Engagement of CD43 enhances human immunodeficiency virus type 1 transcriptional activity and virus production that is induced upon TCR/CD3 stimulation [2].
• Pancreatic elastase and Staphylococcus aureus V8 protease cleave CD43 at discrete extracellular sites [3].
• These new anti-CD43 antibodies are likely to prove useful as screening tools in the detection of colorectal adenomas [4].

Psychiatry related information on SPN

• The physician's role in the management of a patient with an SPN is to educate and advise [5].
• This suggests that 5-HT neurons may lower the threshold of SPN to sympathetic inputs during states of wakefulness [6].
• Expression of CD43 in human microglia and its downregulation in Alzheimer's disease [7].

High impact information on SPN

• Enhancement of T-cell activation by the CD43 molecule whose expression is defective in Wiskott-Aldrich syndrome [8].
• Anti-CD43 monoclonal antibodies have a modest costimulatory effect on T cells, natural killer cells, B cells and monocytes, and one such antibody has been shown to activate T cells directly [8].
• We also found that antigen-presenting cells can bind specifically to immobilized purified CD43 and that the binding can be inhibited by liposomes containing CD43 as well as by anti-CD43 monoclonal antibodies [8].
• To investigate a possible physiological role for CD43, a complementary DNA encoding the human protein was introduced into an antigen-responsive murine T-cell hybridoma [8].
• Here, we demonstrate that TCR-induced exclusion of the large sialoprotein CD43 from the synapse is an active event mediated by its reversible binding to moesin [9].

Chemical compound and disease context of SPN

• Histological examination showed fibromuscular hyperplasia with dense infiltration by myelomonocytes which stained positively with chloroacetate esterase; immunohistochemical staining was positive for lysozyme, CD43, CD45, and CD68 [10].
• Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes [11].
• Inhibition of NF-kappaB activation and chemokine expression by the leukocyte glycoprotein, CD43, in colon cancer cells [12].
• Five antibodies, MT1 (CD43), UCHL1 (CD45RO), OPD4, poly-CD3 and beta F1, were assessed for their reactivity with 50 archival cases of T-cell lymphoma in formalin-fixed paraffin-embedded tissue [13].

Biological context of SPN

• Here we describe the cDNA cloning and derived amino acid sequence of human sialophorin [14].
• Here we report that a dramatic down-regulation of CD43 mRNA levels occurs during activation of the leukocytic cell line K562 [15].
• However, during leukocyte activation CD43 expression is repressed, facilitating the intercellular contact required for chemotaxis, phagocytosis, aggregation, adhesion to endothelium, and transendothelial migration [15].
• Videomicroscopy analysis of homotypic cell aggregation induced through CD43 showed that cellular uropods mediate cell-cell contacts and lymphocyte recruitment [16].
• CD25(high) DC(ims) showed significant up-regulation of the DC activation molecule CD43 and induced increased levels of IL-2 secretion in allogeneic T-cells (170.7+/-86.7pg/mL) as compared to T-cells coincubated with CD25(low) DC(ims) (86.6+/-37.6pg/mL) [p=0.0224] [17].

Anatomical context of SPN

• WAS T cell lines thus do not express defects in CD43 (decreased amount, abnormal molecular weight), previously documented in WAS circulating lymphocytes [18].
• Molecular characterization of sialophorin (CD43), the lymphocyte surface sialoglycoprotein defective in Wiskott-Aldrich syndrome [14].
• When leukocytes are at rest, CD43 acts to prevent both homotypic and heterotypic interactions [15].
• The polarization and homotypic cell aggregation induced through CD43 was prevented by butanedione monoxime, indicating the involvement of myosin cytoskeleton in these phenomena [16].
• Leukosialin (CD43) defines hematopoietic progenitors in human embryonic stem cell differentiation cultures [19].

Associations of SPN with chemical compounds

• Comparison of peptide sequences from the native galactoglycoprotein and the deglycosylated derivative demonstrated the locations of 25 sites of O-glycosylation and three serine sites that are not glycosylated [20].
• In this report, we show that CD43, a sialomucin expressed constitutively on T cells, can also be decorated with the CLA epitope and serve as an E-selectin ligand [21].
• T cell activation through the CD43 molecule leads to Vav tyrosine phosphorylation and mitogen-activated protein kinase pathway activation [22].
• Pretreatment with sialidase enhances sensitivity 13-fold for trypsin, 40-fold for S. aureus V8 protease, and 400-fold for elastase, suggesting that sialic acid influences the survival of surface CD43 molecules when cells are exposed to protease [3].
• Consistent with the transient CD43-dependent intracellular Ca(2+) peaks reported by others, signals generated through the CD43 molecule resulted in the induction of NF-AT DNA binding activity [23].

Physical interactions of SPN

• CD43 interacts with moesin and ezrin and regulates its redistribution to the uropods of T lymphocytes at the cell-cell contacts [16].
• Finally, sialoadhesin bound different glycoforms of CD43 expressed in Chinese hamster ovary cells, including unbranched (core 1) and branched (core 2) O:-linked glycans, that are normally found on CD43 in resting and activated T cells, respectively [24].
• CD43-mediated signals induce DNA binding activity of AP-1, NF-AT, and NFkappa B transcription factors in human T lymphocytes [23].
• Moreover, galectin-1 binding clustered CD43 modified with either core 1 or core 2 O-glycans on the T cell surface [25].
• Provided that the coreceptor molecule CD43 is a very abundant molecule evenly distributed on the membrane of T cell surface protruding 45 nm from the cell, we hypothesized that CD43 is one of the first molecules that interacts with the APC and thus modulates TCR activation [26].

Enzymatic interactions of SPN

• Flow cytometry showed that neutrophil CD43 is cleaved by low levels of neutrophil elastase with half-maximal cleavage at 5 micrograms/mL; pancreatic elastase, in contrast, did not cleave CD43 [27].

Regulatory relationships of SPN

• hnRNP-K and Pur(alpha) act together to repress the transcriptional activity of the CD43 gene promoter [15].
• CD43 expressed in COS cells supported increased binding to immobilized sialoadhesin [24].
• Pro-activatory anti-CD43 monoclonal antibody (MoAb) induced polarization of T lymphocytes with redistribution of CD43 to the uropod and the CCR2 chemokine receptor to the leading edge of the cell [16].
• Taken together, these findings suggest that the CD43 molecules expressed on CD4+ memory T cells may be capable of enhancing the costimulatory signaling and hence providing accessory functions to TCR-mediated activation processes [28].
• CD43-mediated apoptosis was enhanced by coimmobilized anti-CD45 mAb and partly suppressed by coimmobilized anti-CD50 (ICAM-3) or anti-CD99 mAb [29].

Other interactions of SPN

• Immunofluorescence microscopy performed in parallel showed that uropods enriched in CD43 and moesin localized at the cell-cell contact areas of cell aggregates [16].
• We have determined that heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and Pur(alpha) act together to mediate repression of the CD43 promoter during K562 activation [15].
• The size of the synaptic cleft and distinct distributions of filamentous actin, ezrin, CD43, and CD45 at activating and inhibitory human NK cell immune synapses [30].
• Cutting edge: CD43 functions as a T cell counterreceptor for the macrophage adhesion receptor sialoadhesin (Siglec-1) [24].
• Down-regulation by tumor necrosis factor-alpha of neutrophil cell surface expression of the sialophorin CD43 and the hyaluronate receptor CD44 through a proteolytic mechanism [31].

Analytical, diagnostic and therapeutic context of SPN

• Immunofluorescence analysis showed that all three ezrin-radixin-moesin (ERM) actin-binding proteins localized in the uropod of both human T lymphoblasts stimulated with anti-CD43 MoAb and tumor-infiltrating T lymphocytes [16].
• Here, using hESC differentiation in coculture with OP9 stromal cells, we demonstrate that early progenitors committed to hematopoietic development could be identified by surface expression of leukosialin (CD43) [19].
• With regard to cancer vaccination protocols, we propose to use CD25 and CD43 as additional markers for DC quality control, assessment of maturational status, and positive selection [17].
• Further support of the relatedness of these molecules was obtained by immunoprecipitation of 125I-labeled galactoglycoprotein by monoclonal anti-CD43 antibodies [20].
• These studies identify nuclear factor-kappaB (NF-kappaB) p65 serine 468 as a novel inducible phosphorylation site strongly induced by T-cell costimulation and only weakly triggered by CD43 ligation [32].

References