Identification of granulocyte subtype-selective receptors and ion channels by using a high-density oligonucleotide probe array

被引:34
作者
Nakajima, T
Iikura, M
Okayama, Y
Matsumoto, K
Uchiyama, C
Shirakawa, T
Yang, X
Adra, CN
Hirai, K
Saito, H
机构
[1] Natl Res Inst Child Hlth & Dev, Dept Allergy & Immunol, Setagaya Ku, Tokyo 1548567, Japan
[2] Harvard Univ, Sch Med, Childrens Hosp, Dept Med, Boston, MA USA
[3] Beth Israel Deaconess Med Ctr, Dept Pathol & Med, Boston, MA 02215 USA
[4] Kyoto Univ, Grad Sch Publ Hlth, Dept Hlth Promot & Human Behav, Kyoto, Japan
[5] RIKEN, Res Ctr Allergy & Immunol, Lab Allergy & Immunol, Yokohama, Kanagawa, Japan
[6] Univ Tokyo, Grad Sch Med, Dept Bioregulat Funct, Tokyo, Japan
[7] Org Pharmaceut Safety & Res, Tokyo, Japan
关键词
basophils; eosinophils; granulocytes; G protein-coupled receptors; ion channels;
D O I
10.1016/j.jaci.2003.12.036
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: During inflammation, neutrophils, basophils, and eosinophils release cell type-specific mediators and proteases through signaling molecules, such as G protein-coupled receptors and ion channels. As such, ion channels and receptors, including G protein-coupled receptors, are common drug targets. Objective: We sought to identify, for the first time, ion channels and receptors preferentially expressed by each granulocyte subtype. Methods: Using GeneChip, we compared approximately 20,000 transcripts present in 7 leukocyte types, platelets, mast cells, and fibroblasts to identify granulocyte subtype-selective transcripts for receptors and ion channels. Granulocyte subtype-selective transcripts were chosen on the basis of several conditions, such as the transcript having a 5-fold or greater expression level compared with the maximum level of other leukocytes. Results: Fifty-one transcripts were chosen to be preferentially expressed by each granulocyte subtype. Seventeen of the 51 transcripts have not been previously reported as granulocyte subtype selective. Among the 17 receptors and ion channels, 6 were basophil selective, eosinophil selective, or both and were not highly expressed by other organs, indicating that they might be potential targets for antiallergy drugs. Conclusion: Use of this database of potential cell type-selective drug targets should minimize the efforts required for pharmaceutical development.
引用
收藏
页码:528 / 535
页数:8
相关论文
共 37 条
[1]   CLONING OF THE CDNA FOR A HEMATOPOIETIC CELL-SPECIFIC PROTEIN RELATED TO CD20 AND THE BETA-SUBUNIT OF THE HIGH-AFFINITY IGE RECEPTOR - EVIDENCE FOR A FAMILY OF PROTEINS WITH 4 MEMBRANE-SPANNING REGIONS [J].
ADRA, CN ;
LELIAS, JM ;
KOBAYASHI, H ;
KAGHAD, M ;
MORRISON, P ;
ROWLEY, JD ;
LIM, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (21) :10178-10182
[2]   Chromosome 11q13 and atopic asthma [J].
Adra, CN ;
Mao, XQ ;
Kawada, H ;
Gao, PS ;
Korzycka, B ;
Donate, JL ;
Shaldon, SR ;
Coull, P ;
Dubowitz, M ;
Enomoto, T ;
Ozawa, A ;
Syed, SA ;
Horiuchi, T ;
Khaeraja, R ;
Khan, R ;
Lin, SR ;
Flinter, F ;
Beales, P ;
Hagihara, A ;
Inoko, H ;
Shirakawa, T ;
Hopkin, JM .
CLINICAL GENETICS, 1999, 55 (06) :431-437
[3]  
Arock M, 2002, J LEUKOCYTE BIOL, V71, P557
[4]   Road signs guiding leukocytes along the inflammation superhighway [J].
Bochner, BS .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2000, 106 (05) :817-828
[5]   Ion channel gene expression in human lung, skin, and cord blood-derived mast cells [J].
Bradding, P ;
Okayama, Y ;
Kambe, N ;
Saito, H .
JOURNAL OF LEUKOCYTE BIOLOGY, 2003, 73 (05) :614-620
[6]  
CHURCH MK, 1982, J IMMUNOL, V129, P2116
[7]   Human HTm4 is a hematopoietic cell cycle regulator [J].
Donato, JL ;
Ko, J ;
Kutok, JL ;
Cheng, T ;
Shirakawa, T ;
Mao, XQ ;
Beach, D ;
Scadden, DT ;
Sayegh, MH ;
Adra, CN .
JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (01) :51-58
[8]   Drug discovery: A historical perspective [J].
Drews, J .
SCIENCE, 2000, 287 (5460) :1960-1964
[9]  
Fukagawa K, 2002, INVEST OPHTH VIS SCI, V43, P58
[10]   Human neutrophils express the high-affinity receptor for immunoglobulin E (FcεRI):: role in asthma [J].
Gounni, AS ;
Lamkhioued, B ;
Koussih, L ;
Ra, C ;
Renzi, PM ;
Hamid, Q .
FASEB JOURNAL, 2001, 15 (06) :940-949