Immune system expression of SLURP-1 and SLURP-2, two endogenous nicotinic acetylcholine receptor ligands.
A novel transduction pathway via which apoptosis of keratinocytes is regulated through nicotinic acetylcholine (ACh) receptors (nAChRs) has emerged in studies of secreted mammalian Ly6/urokinase plasminogen-type activator receptor-related protein-1 and-2 (SLURP-1 and SLURP-2, respectively). SLURP-1 reportedly binds to alpha7 nAChRs and enhances the amplitude of macroscopic currents induced by ACh, leading to facilitation of apoptosis, whereas SLURP-2 binds to alpha3 nAChRs and prevents apoptosis. These observations prompted us to test whether SLURPs are expressed in immune cells and are involved in the regulation of immune function. We initially used reverse transcription-polymerase chain reaction analysis to characterize the expression profiles of SLURP mRNAs in several murine tissues and organs. Although SLURP-1 mRNA was not expressed in the pancreas, all other tissues and organs tested, including spleen and thymus, expressed both SLURP-1 and SLURP-2 mRNAs. Expression of both mRNAs also was detected in T and B cells, bone marrow-derived dendritic cells (DCs) and macrophages. Moreover, as in keratinocytes, stimulation of MOLT-3 human leukemic T cells with recombinant human SLURP-1 evoked intracellular Ca(2+) signaling. These results suggest that both SLURP-1 and SLURP-2 are expressed in various immune cells and organs, and that not only ACh but also SLURPs may be involved in regulating lymphocyte function via nAChR-mediated pathways.
Moriwaki
Yasuhiro
Y
Department of Pharmacology, Kyoritsu College of Pharmacy, 1-5-30 Shibakoen, Tokyo 105-8512, Japan.
Yoshikawa
Ken
K
Fukuda
Hiromi
H
Fujii
Yoshihito X
YX
Misawa
Hidemi
H
Kawashima
Koichiro
K
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics*; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000378:metabolism; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling; D006801:Humans; D007107:Immune System / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D000950:Antigens, Ly; D058851:GPI-Linked Proteins; C485626:LYNX1 protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C048963:SLURP1 protein, human; D014568:Urokinase-Type Plasminogen Activator