Induction of lysosomal and plasma membrane-bound sialidases in human T-cells via T-cell receptor.
Among the three isoenzymes of neuraminidase (Neu) or sialidase, Neu-1 has been suggested to be induced by cell activation and to be involved in IL (interleukin)-4 biosynthesis in murine T-cells. In the present study, we found that antigen-induced airway eosinophilia, a typical response dependent on Th2 (T-helper cell type 2) cytokines, as well as mRNA expression of Th2 cytokines, including IL-4, are suppressed in Neu-1-deficient mice, thereby demonstrating the in vivo role of murine Neu-1 in regulation of Th2 cytokines. To elucidate the roles of various sialidases in human T-cell activation, we investigated their tissue distribution, gene induction and function. Neu-1 is the predominant isoenzyme at the mRNA level in most tissues and cells in both mice and humans, including T-cells. T-cells also have significant levels of Neu-3 mRNAs, albeit much lower than those of Neu-1, whereas the levels of Neu-2 mRNAs are minimal. In human T-cells, both Neu-1 and Neu-3 mRNAs are significantly induced by T-cell-receptor stimulation, as is sialidase activity against 4-methylumbelliferyl- N -acetylneuramic acid (a substrate for both Neu-1 and Neu-3) and the ganglioside G(D1a) [NeuAcalpha2-3Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-4Glcbeta1-cer] (a substrate for Neu-3, but not for Neu-1). The expression of the two sialidase genes may be under differential regulation. Western blot analysis and enzymic comparison with recombinant sialidases have revealed that Neu-3 is induced as a major isoform in activated cells. The induction of Neu-1 and Neu-3 in T-cells is unique. In human monocytes and neutrophils stimulated with various agents, the only observation of sialidase induction has been by IL-1 in neutrophils. Functionally, a major difference has been observed in Jurkat T-cell lines over-expressing Neu-1- and Neu-3. Upon T-cell receptor stimulation, IL-2, interferon-gamma, IL-4 and IL-13 are induced in the Neu-1 line, whereas in the Neu-3 line the same cytokines are induced, with the exception of IL-4. Taken together, these results suggest an important immunoregulatory role for both Neu-1 and Neu-3 in humans.
Allergy Department, Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-1600, Kenilworth, NJ 07033, USA. peng.wang@spcorp.com
Peng
P
Wang
Ji
J
Zhang
Hong
H
Bian
Ping
P
Wu
Reshma
R
Kuvelkar
Ted T
TT
Kung
Yvette
Y
Crawley
Robert W
RW
Egan
M Motasim
MM
Billah
D000818:Animals; D018106:CD28 Antigens / Q000494:pharmacology; D017252:CD3 Complex / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology*; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D004802:Eosinophilia / Q000209:etiology / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D007313:Insecta / Q000166:cytology; D007527:Isoenzymes / Q000096:biosynthesis / Q000502:physiology; D019169:Jurkat Cells / Q000201:enzymology; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008213:Lymphocyte Activation / Q000502:physiology; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009439:Neuraminidase / Q000096:biosynthesis* / Q000172:deficiency / Q000502:physiology; D009928:Organ Specificity / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D015533:Transcriptional Activation
D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D007527:Isoenzymes; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; C486385:NEU1 protein, human; C403285:NEU2 protein, human; C110128:Neu1 protein, mouse; C465436:Neu3 protein, human; D009439:Neuraminidase