Article (Scientific journals)
Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidime.
Mathy, Marianne; Deby, Ginette; Deby, C. et al.
1995In Mediators of Inflammation, 4 (6), p. 437-43
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Keywords :
Myeloperoxidase; oxidant stress; endothelial cells; hypochlorous acid; Ceftazidime; Antibiotics
Abstract :
[en] We investigated the effects of the antibiotic ceftazidime (CAZ) on the cytolytic action of the neutrophil myeloperoxidase-hydrogen peroxide-chloride anion system (MPO/H(2)O(2)/Cl(-)). In this system, myeloperoxidase catalyses the conversion of H(2)O(2) and CI(-) to the cytotoxic agent HOCl. Stimulated neutrophils can release MPO into the extracellular environment and then may cause tissue injury through direct endothelial cells lysis. We showed that human umbilical vein endothelial cells (HUVEC) were capable of taking up active MPO. In presence of H(2)O(2) (10(-4) M), this uptake was accompanied by cell lysis. The cytolysis was estimated by the release of (51)Cr from HUVEC and expressed as an index of cytotoxicity (IC). Dose dependent protection was obtained for CAZ concentrations ranging from 10(-5) to 10(-3) M;this can be attributed to inactivation of HOCl by the drug. This protection is comparable to that obtained with methionine and histidine, both of which are known to neutralize HOCl. This protection by CAZ could also be attributed to inactivation of H(2)O(2), but when cytolysis was achieved with H(2)O(2) or O(2) (-) generating enzymatic systems, no protection by CAZ was observed. Moreover, the peroxidation activity of MPO (action on H(2)O(2)) was not affected by CAZ, while CAZ prevented the chlorination activity of MPO (chlorination of monochlorodimedon). So, we concluded that CAZ acts via HOCl inactivation. These antioxidant properties of CAZ may be clinically useful in pathological situations where excessive activation of neutrophils occurs, such as in sepsis.
Disciplines :
Immunology & infectious disease
Anesthesia & intensive care
Author, co-author :
Mathy, Marianne ;  Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
Deby, Ginette ;  Université de Liège - ULiège > Centre de l'oxygène : Recherche et développement (C.O.R.D.)
Deby, C.
Jadoul, L.
Vandenberghe, A.
Lamy, Maurice ;  Centre Hospitalier Universitaire de Liège - CHU > Anesthésie et réanimation
Language :
English
Title :
Cytotoxicity towards human endothelial cells, induced by neutrophil myeloperoxidase: protection by ceftazidime.
Publication date :
1995
Journal title :
Mediators of Inflammation
ISSN :
0962-9351
eISSN :
1466-1861
Publisher :
Hindawi Publishing Corporation, Sylvania, United States - Ohio
Volume :
4
Issue :
6
Pages :
437-43
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 25 March 2009

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