Antiproteases modulate bronchial epithelial cell responses to endotoxin

S. Koyama, Stephen Israel Rennard, L. Claassen, R. A. Robbins

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Escherichia coli endotoxin (0.1 to 1000 μg/ml) stimulated the release of neutrophil chemotactic activity (P < 0.001) and induced bronchial epithelial cell (BEC) cytotoxicity assessed by lactate dehydrogenase release (P < 0.001). Endotoxin (100 μg/ml) inhibited BEC accumulation (P < 0.001). In the present study, we investigated the role of proteolytic activity of BECs per se in response to endotoxin. Several structurally and functionally different antiproteases, α1 protease inhibitor, soybean trypsin inhibitor, two chloromethyl ketone derivatives (N-tosyl-L-lysine chloromethyl ketone and methoxysuccinyl-Ala-Ala-Pro-Val chloromethyl ketone), and L-658,758, a neutrophil elastase inhibitor, attenuated the release of neutrophil chemotactic activity and lactate dehydrogenase (P < 0.01). α1-Protease inhibitor and N-tosyl-L-lysine chloromethyl ketone attenuated the inhibition of BEC accumulation by endotoxin (P < 0.001). The proteolytic enzyme activity measured by synthetic substrates revealed that endotoxin significantly augmented the serine proteolytic activity in the cell layers. Culture supernatant fluids and cell lysates of BECs in the presence of endotoxin solubilized 14C-labeled casein. These data suggest that responses of BECs to endotoxin may involve activation of cellular proteolytic activity.

Original languageEnglish (US)
Pages (from-to)1207-1219
Number of pages13
JournalAmerican Journal of Pathology
Volume146
Issue number5
StatePublished - Jan 1 1995

Fingerprint

Protease Inhibitors
Endotoxins
Epithelial Cells
L 658758
L-Lactate Dehydrogenase
Lysine
Neutrophils
Secretory Proteinase Inhibitory Proteins
Trypsin Inhibitors
Caseins
Ketones
Soybeans
Serine
Peptide Hydrolases

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Koyama, S., Rennard, S. I., Claassen, L., & Robbins, R. A. (1995). Antiproteases modulate bronchial epithelial cell responses to endotoxin. American Journal of Pathology, 146(5), 1207-1219.

Antiproteases modulate bronchial epithelial cell responses to endotoxin. / Koyama, S.; Rennard, Stephen Israel; Claassen, L.; Robbins, R. A.

In: American Journal of Pathology, Vol. 146, No. 5, 01.01.1995, p. 1207-1219.

Research output: Contribution to journalArticle

Koyama, S, Rennard, SI, Claassen, L & Robbins, RA 1995, 'Antiproteases modulate bronchial epithelial cell responses to endotoxin', American Journal of Pathology, vol. 146, no. 5, pp. 1207-1219.
Koyama S, Rennard SI, Claassen L, Robbins RA. Antiproteases modulate bronchial epithelial cell responses to endotoxin. American Journal of Pathology. 1995 Jan 1;146(5):1207-1219.
Koyama, S. ; Rennard, Stephen Israel ; Claassen, L. ; Robbins, R. A. / Antiproteases modulate bronchial epithelial cell responses to endotoxin. In: American Journal of Pathology. 1995 ; Vol. 146, No. 5. pp. 1207-1219.
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