Antibacterial activity of apical surface fluid from the human airway cell line Calu-3: pharmacologic alteration by corticosteroids and beta(2)-agonists.
Calu-3 cells, a human lung carcinoma cell line with properties like serous cells of the upper airway, were used to develop an in vitro model for airway antibacterial activity. Calu-3 cell monolayers were cultured on permeable supports at an air-liquid interface. Apical surface fluid (ASF) was collected by washing; antibacterial activity was assayed by incubating ASF washings with bacteria for 18 h and counting surviving colony-forming units. ASF washings killed Escherichia coli and Pseudomonas aeruginosa. Antibacterial activity was salt sensitive and dependent on protein concentration. After washing, approximately 30 h were required before antibacterial activity recovered to its initial level. After culturing with topical corticosteroids (budesonide, triamcinolone, or beclomethasone, 0.1 microg/ml for 48 h), ASF antibacterial activity was 4- to 10-fold greater than the ASF from control monolayers. The increase in antibacterial activity was dose-dependent. The beta(2)-agonists salbutamol and terbutaline (100 microg/ml for 48 h) decreased ASF antibacterial activity by 5- to 8-fold. The nonsteroidal anti-inflammatory agents ibuprofen and cromolyn sodium had no effect. Our results are most consistent with agonist-dependent changes in the composition of ASF antibacterial proteins. We conclude that Calu-3 cells synthesize and secrete antibacterial proteins and that clinical agents can alter these functions.
Zhang
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Department of Medical and Clinical Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803, USA.
Reenstra
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WW
Chidekel
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A
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D001483:Base Sequence; D001826:Body Fluids / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism* / Q000382:microbiology
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D000900:Anti-Bacterial Agents; D017931:DNA Primers; D011506:Proteins; D012333:RNA, Messenger