Gene Expression Profiling of Human Mast Cell Subtypes: An In Silico Study.

BACKGROUND Human mast cells (MCs) were classified into at least two subtypes, i.e., tryptase- and chymase-positive MCs (MCtc) and tryptase-only-positive MCs (MCt). However, differences in global molecular expression between these subtypes are unknown. METHODS We analyzed public microarray data of MC subtypes derived from various tissues and those of peripheral blood granulocytes by using hierarchical clustering methods to understand the global gene expression profiles. RESULTS All the transcripts subjected to this clustering analysis were classified into two large clusters, i.e., MC- preferential or granulocyte-preferential. In the original works, MCs from tonsil, lung and skin had been cultured for more than several weeks to obtain highly viable and pure cell populations, and these MCs retained their typical profiles such as intensities of chymase protein expression. Most of the transcripts were commonly expressed by these MC subtypes. However, tonsil-derived MCs and skin-derived MCs but not lung-derived MCs expressed high levels of chymase (CMA1) as expected for the properties of MCtc and MCt. These CMA1-high MCs and CMA1 -low MCs respectively expressed distinct sets of transcripts as small gene clusters as well as CMA-1 even after being cultured in the absence of a tissue environment. CONCLUSIONS The MC lineage seems to be far from the granulocyte lineages including basophils. CMA1-high MCs (MCtc) and CMA1-low MCs (MCt) can be regarded as differentiated MC subtypes. As such, importance of data analysis studies will be increasing along with the accumulation of global molecular data in the public database.

[1]  J. Abe,et al.  Allergy-related genes in microarray: an update review. , 2005, The Journal of allergy and clinical immunology.

[2]  Wei Zhao,et al.  Surface CD88 functionally distinguishes the MCTC from the MCT type of human lung mast cell. , 2005, The Journal of allergy and clinical immunology.

[3]  P. Lipsky,et al.  Analysis of the lineage relationship between mast cells and basophils using the c-kit D816V mutation as a biologic signature. , 2005, The Journal of allergy and clinical immunology.

[4]  T. Fukuda,et al.  FcεRI-mediated amphiregulin production by human mast cells increases mucin gene expression in epithelial cells , 2005 .

[5]  Y. Okayama,et al.  T Cell Proliferation by Direct Cross-Talk between OX40 Ligand on Human Mast Cells and OX40 on Human T Cells: Comparison of Gene Expression Profiles between Human Tonsillar and Lung-Cultured Mast Cells1 , 2004, The Journal of Immunology.

[6]  Y. Okayama,et al.  Identification of granulocyte subtype-selective receptors and ion channels by using a high-density oligonucleotide probe array. , 2004, The Journal of allergy and clinical immunology.

[7]  H. Hirata,et al.  The Basic Helix-Loop-Helix Genes Hesr1/Hey1 and Hesr2/Hey2 Regulate Maintenance of Neural Precursor Cells in the Brain* , 2003, Journal of Biological Chemistry.

[8]  Y. Okayama,et al.  Identification of specific gene expression profiles in human mast cells mediated by Toll-like receptor 4 and FcepsilonRI. , 2003, Blood.

[9]  Eric M. Billings,et al.  F(ab)′2-mediated neutralization of C3a and C5a anaphylatoxins: a novel effector function of immunoglobulins , 2003, Nature Medicine.

[10]  P. Hunter,et al.  Integration from proteins to organs: the Physiome Project , 2003, Nature Reviews Molecular Cell Biology.

[11]  G. Tsujimoto,et al.  Marked increase in CC chemokine gene expression in both human and mouse mast cell transcriptomes following Fcepsilon receptor I cross-linking: an interspecies comparison. , 2002, Blood.

[12]  Duccio Cavalieri,et al.  Standards for Microarray Data , 2002, Science.

[13]  J. Kochan,et al.  Human skin-derived mast cells can proliferate while retaining their characteristic functional and protease phenotypes. , 2001, Blood.

[14]  K. Matsumoto,et al.  Selective down-regulation of high-affinity IgE receptor (FcepsilonRI) alpha-chain messenger RNA among transcriptome in cord blood-derived versus adult peripheral blood-derived cultured human mast cells. , 2001, Blood.

[15]  K. Matsumoto,et al.  Regulation of chymase production in human mast cell progenitors. , 2000, The Journal of allergy and clinical immunology.

[16]  M. Ebisawa,et al.  Characterization of mast cell-committed progenitors present in human umbilical cord blood. , 1999, Blood.

[17]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Suneet Agarwal,et al.  Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. , 1998, Immunity.

[19]  M. Murakami,et al.  Mouse bone marrow-derived mast cells undergo exocytosis, prostanoid generation, and cytokine expression in response to G protein-activating polybasic compounds after coculture with fibroblasts in the presence of c-kit ligand. , 1997, Journal of immunology.

[20]  N. Copeland,et al.  Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles , 1990, Cell.

[21]  C. Elson,et al.  Deficiency of the tryptase-positive, chymase-negative mast cell type in gastrointestinal mucosa of patients with defective T lymphocyte function. , 1987, Journal of immunology.

[22]  J. Denburg,et al.  'Mucosal' mast cells. , 1984, Immunology today.

[23]  J. Ihle,et al.  Biologic properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, p cell-stimulating factor activity, colony-stimulating factor activity, and histamine-producing cell-stimulating factor activity. , 1983, Journal of immunology.

[24]  J. Gauldie,et al.  Mucosal mast cells. I. Isolation and functional characteristics of rat intestinal mast cells. , 1982, Journal of immunology.

[25]  L. Enerbäck,et al.  Mast cells in rat gastrointestinal mucosa. 2. Dye-binding and metachromatic properties. , 1966, Acta pathologica et microbiologica Scandinavica.

[26]  H. Saito Translation of the human genome into clinical allergy, part 2 , 2004 .

[27]  Y. Okayama,et al.  Human mast cell activation through Fc receptors and Toll-like receptors , 2004 .

[28]  H. Saito Translation of the human genome into clinical allergy , 2003 .

[29]  T. Nakahata,et al.  Interleukin-4 promotes the development of tryptase and chymase double-positive human mast cells accompanied by cell maturation. , 1998, Blood.