Expression of SLURP-1, an endogenous alpha7 nicotinic acetylcholine receptor allosteric ligand, in murine bronchial epithelial cells.
Mammalian secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) is a positive allosteric ligand for alpha7 nicotinic acetylcholine (ACh) receptors (alpha7 nAChRs) that potentiates responses to ACh and elicits proapoptotic activity in human keratinocytes. Mutations in the gene encoding SLURP-1 have been detected in patients with Mal de Meleda, a rare autosomal recessive skin disorder characterized by transgressive palmoplantar keratoderma. On the basis of these findings, SLURP-1 is postulated to be involved in regulating tumor necrosis factor-alpha (TNF-alpha) release from keratinocytes and macrophages via alpha7 nAChR-mediated pathways. In the present study, we assessed SLURP-1 expression in lung tissue from C57BL/6J mice to investigate the functions of SLURP-1 in pulmonary physiology and pathology. Immunohistochemical and in situ hybridization analyses revealed expression of SLURP-1 protein and mRNA, respectively, exclusively in ciliated bronchial epithelial cells. This was supported by Western blotting showing the presence of the 9.5-kDa SLURP-1 protein in whole-lung tissue and trachea. In addition, high-affinity choline transporter (CHT1) was detected in apical regions of bronchial epithelial cells and in neurons located in the lamina propria of the bronchus, suggesting that bronchial epithelial cells are able to synthesize both SLURP-1 and ACh. We also observed direct contact between F4/80-positive macrophages and bronchial epithelial cells and the presence of invading macrophages in close proximity to CHT1-positive nerve elements. Collectively, these results suggest that SLURP-1 contributes to the maintenance of bronchial epithelial cell homeostasis and to the regulation of TNF-alpha release from macrophages in bronchial tissue.
Horiguchi
Kazuhide
K
Department of Anatomy, University of Fukui Faculty of Medical Sciences, Matsuoka, Fukui, Japan.
Horiguchi
Satomi
S
Yamashita
Naomi
N
Irie
Kaoru
K
Masuda
Junya
J
Takano-Ohmuro
Hiromi
H
Himi
Toshiyuki
T
Miyazawa
Mai
M
Moriwaki
Yasuhiro
Y
Okuda
Takashi
T
Misawa
Hidemi
H
Ozaki
Hiroshi
H
Kawashima
Koichiro
K
D000109:Acetylcholine / Q000096:biosynthesis; D000494:Allosteric Regulation / Q000502:physiology; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D002799:Cholinergic Fibers / Q000378:metabolism; D007150:Immunohistochemistry; D008024:Ligands; D008264:Macrophages / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000950:Antigens, Ly; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D008024:Ligands; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; C545249:SLURP-1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; C065637:choline transporter; D014568:Urokinase-Type Plasminogen Activator; D000109:Acetylcholine