Secretion and gene expression of secretory leukocyte protease inhibitor by human airway submucosal glands.
Submucosal glands were isolated within 4 h of death from tracheae and bronchi obtained from autopsied lungs, and the secretory response of secretory leukocyte protease inhibitor (SLPI) was examined with ELISA and a secretory index. Although human neutrophil elastase (HNE) at low concentrations increased SLPI secretion above the control level (i.e., 149% of control level at 10(-11) M), HNE at high concentrations significantly decreased it below the control level (i.e., 16% of control level at 10(-7) M). The decrease in SLPI concentration was shown to result from the degradation of SLPI by excessive HNE. Methacholine induced significant secretion (i.e., 363% of control level at 10(-5) M) that was abolished by both M(1) and M(3) receptor antagonists. A semiquantitative analysis of SLPI mRNA by RT-PCR and Southern blot showed that compared with the superficial epithelium, submucosal glands had a 30-fold or higher level of SLPI mRNA. Both HNE and methacholine significantly increased the level of SLPI mRNA in submucosal glands in a dose-dependent manner (i.e., 357% of control level at 10(-7) M and 175% of control level at 10(-5) M, respectively). These findings indicate that human airway submucosal glands can transcribe 30-fold or more SLPI mRNA than the superficial epithelium and that SLPI mRNA transcription and secretion are regulated by both HNE and muscarinic receptors.
Saitoh
H
H
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai 980-8574, Japan.
Masuda
T
T
Shimura
S
S
Fushimi
T
T
Shirato
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005088:Exocrine Glands / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D053481:Secretory Leukocyte Peptidase Inhibitor; D014132:Trachea
D005938:Glucocorticoids; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012333:RNA, Messenger; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D016210:Methacholine Chloride; D010890:Pirenzepine; D001285:Atropine; D003907:Dexamethasone; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D019272:Leukocyte Elastase; C048593:otenzepad