Tags

Type your tag names separated by a space and hit enter

Mechanism of neutrophil-induced xanthine dehydrogenase to xanthine oxidase conversion in endothelial cells: evidence of a role for elastase.
Am J Respir Cell Mol Biol. 1992 Mar; 6(3):270-8.AJ

Abstract

Activated neutrophils cause conversion of xanthine dehydrogenase to its oxidase form (xanthine oxidase) in endothelial cells, the mechanism of which may be related to the cytotoxic effect of activated neutrophils. The elastase inhibitors, elastatinal, alpha 1-antitrypsin, and MeO-Suc-(Ala)2-Pro-Val-CH2Cl, significantly inhibited xanthine dehydrogenase to oxidase conversion by phorbol myristate acetate-stimulated neutrophils without inhibition of neutrophil adherence to the endothelial cell monolayer. The role of elastase in this enzyme conversion process was confirmed by the ability of purified elastase to cause conversion of xanthine dehydrogenase to xanthine oxidase in intact endothelial cells (or cell extracts) without causing cytotoxicity. In contrast, cathepsin G failed to cause conversion. The kinetics of conversion induced by elastase was relatively rapid, being essentially completed by 30 min. Upon removal of elastase, the effect was slowly (greater than 12 h) reversible and could be inhibited by cycloheximide treatment. Exposure of endothelial cells to hypoxia failed to enhance the elastase-induced conversion. Treatment of endothelial cells with Ca2+ ionophores failed to cause conversion of xanthine dehydrogenase to oxidase, suggesting that intracellular Ca(2+)-activated proteases are not sufficient to induce this process. Neutrophil-induced xanthine dehydrogenase to oxidase conversion was inhibited by concomitant treatment with antibodies to CD11b. The results suggest that activated neutrophils induce conversion of xanthine dehydrogenase to oxidase by secretion of elastase in close proximity to the endothelial cells and that this intimate contact between the two cell types enables high local concentrations of elastase to be attained, which are sufficient to cause xanthine dehydrogenase to xanthine oxidase conversion.

Authors+Show Affiliations

Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1540391

Citation

Phan, S H., et al. "Mechanism of Neutrophil-induced Xanthine Dehydrogenase to Xanthine Oxidase Conversion in Endothelial Cells: Evidence of a Role for Elastase." American Journal of Respiratory Cell and Molecular Biology, vol. 6, no. 3, 1992, pp. 270-8.
Phan SH, Gannon DE, Ward PA, et al. Mechanism of neutrophil-induced xanthine dehydrogenase to xanthine oxidase conversion in endothelial cells: evidence of a role for elastase. Am J Respir Cell Mol Biol. 1992;6(3):270-8.
Phan, S. H., Gannon, D. E., Ward, P. A., & Karmiol, S. (1992). Mechanism of neutrophil-induced xanthine dehydrogenase to xanthine oxidase conversion in endothelial cells: evidence of a role for elastase. American Journal of Respiratory Cell and Molecular Biology, 6(3), 270-8.
Phan SH, et al. Mechanism of Neutrophil-induced Xanthine Dehydrogenase to Xanthine Oxidase Conversion in Endothelial Cells: Evidence of a Role for Elastase. Am J Respir Cell Mol Biol. 1992;6(3):270-8. PubMed PMID: 1540391.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanism of neutrophil-induced xanthine dehydrogenase to xanthine oxidase conversion in endothelial cells: evidence of a role for elastase. AU - Phan,S H, AU - Gannon,D E, AU - Ward,P A, AU - Karmiol,S, PY - 1992/3/1/pubmed PY - 1992/3/1/medline PY - 1992/3/1/entrez SP - 270 EP - 8 JF - American journal of respiratory cell and molecular biology JO - Am J Respir Cell Mol Biol VL - 6 IS - 3 N2 - Activated neutrophils cause conversion of xanthine dehydrogenase to its oxidase form (xanthine oxidase) in endothelial cells, the mechanism of which may be related to the cytotoxic effect of activated neutrophils. The elastase inhibitors, elastatinal, alpha 1-antitrypsin, and MeO-Suc-(Ala)2-Pro-Val-CH2Cl, significantly inhibited xanthine dehydrogenase to oxidase conversion by phorbol myristate acetate-stimulated neutrophils without inhibition of neutrophil adherence to the endothelial cell monolayer. The role of elastase in this enzyme conversion process was confirmed by the ability of purified elastase to cause conversion of xanthine dehydrogenase to xanthine oxidase in intact endothelial cells (or cell extracts) without causing cytotoxicity. In contrast, cathepsin G failed to cause conversion. The kinetics of conversion induced by elastase was relatively rapid, being essentially completed by 30 min. Upon removal of elastase, the effect was slowly (greater than 12 h) reversible and could be inhibited by cycloheximide treatment. Exposure of endothelial cells to hypoxia failed to enhance the elastase-induced conversion. Treatment of endothelial cells with Ca2+ ionophores failed to cause conversion of xanthine dehydrogenase to oxidase, suggesting that intracellular Ca(2+)-activated proteases are not sufficient to induce this process. Neutrophil-induced xanthine dehydrogenase to oxidase conversion was inhibited by concomitant treatment with antibodies to CD11b. The results suggest that activated neutrophils induce conversion of xanthine dehydrogenase to oxidase by secretion of elastase in close proximity to the endothelial cells and that this intimate contact between the two cell types enables high local concentrations of elastase to be attained, which are sufficient to cause xanthine dehydrogenase to xanthine oxidase conversion. SN - 1044-1549 UR - https://www.unboundmedicine.com/medline/citation/1540391/Mechanism_of_neutrophil_induced_xanthine_dehydrogenase_to_xanthine_oxidase_conversion_in_endothelial_cells:_evidence_of_a_role_for_elastase_ L2 - https://www.atsjournals.org/doi/10.1165/ajrcmb/6.3.270?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -