Top

Published in:

01-08-2005 | Brief Report

Differential inducible nitric oxide synthase activity in circulating neutrophils vs. mononuclears of septic shock patients

Authors: Moshe Hersch, Jeremy A. Scott, Gabriel Izbicki, David McCormack, Gedeminas Cepinkas, Marlies Ostermann, William J. Sibbald

Published in: Intensive Care Medicine | Issue 8/2005

Abstract

Objective:

To compare nitric oxide synthase (NOS) activity in circulating neutrophils and mononuclear cells of patients with septic shock to healthy subjects.

Design and setting:

Prospective study in the general intensive care unit (30 beds) of a university affiliated-hospital and the A.C. Burton Vascular Biology Research Laboratory.

Patients:

Six septic patients and seven healthy volunteers.

Measurements and results:

We measured NOS in circulating neutrophils and mononuclears. Constitutive (cNOS) and inducible (iNOS) activities were analyzed by the [³H]l-arginine-l-citrulline assay. Plasma NO_x⁻ was determined by chemiluminescence. NO_x⁻ was higher in septic vs. controls (median 110, IQR 39–250 vs. 23, 14–46 µM; p<0.05). cNOS in septic cells was unmeasurable. iNOS in septic neutrophils was higher (median 34.9, IQR 10.4–95.8 vs. controls 2.5, 0–2.7 U; p<0.05) while iNOS in septic mononuclears was unaltered (median 16.4, IQR 9.1–52.6 vs. controls 8.9, 5.9–20.3 U; p=0.240).

Conclusions:

Increased iNOS activity was found in circulating neutrophils of septic shock patients compared to healthy volunteers. Moreover, differential iNOS activity was evident in circulating neutrophils vs. mononuclears of patients with septic shock. Further investigations are warranted to confirm this differential iNOS activity and to explore its significance

Nathan C, Xie QW (1994) Nitric oxide synthases: roles, tolls and controls. Cell 78:915–918CrossRefPubMed

Hibbs JB Jr (1991) Synthesis of nitric oxyde from L-arginine: a recently discovered pathway induced by cytokines with antitumor and antimicrobial activity. Res Immunol 142:565–569CrossRefPubMed

Davies MG, Fulton GJ, Hagen PO (1995) Clinical biology of nitric oxide. Br J Surg 82:1598–1610PubMed

Scott JA, McCormack DG (1999) Selective in vivo inhibition of inducible nitric oxide synthase in a rat model sepsis. J Appl Physiol 86:1739–1745PubMed

Schneeman M, Schoedon G, Hofer S, Blau N, Guerrero L, Shaffner A (1993) Nitric oxide synthase is not a constituent of the antimicrobial armature of the human mononuclear phagocyte. J Infect Dis 167:1358–1363PubMed

Hersch M, Scott Jam Cepinskas G, Ostermann M, Mehta S, McCormack DG, Sibbald WJ (1999) Nitric oxide synthase activities in white cells of septic patients. Crit Care 3 [Suppl 1]:P75

American College of Chest Physicians/Society of Critical Medicine Consensus Conference (1997) Definitions of the systemic inflammatory response syndrome and allied disorders in relation to critically injured patients. Crit Care Med 25:1789–1795PubMed

Kudoh E, Komatu T, Nakaji S, Sugawara K, Kumae T (1992) Investigation of a new method for separation of neutrophils from a small volume of human blood. Nippon Eiseigaku Zasshi 47:650–657PubMed

Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254PubMed

10.

Annane D, Sanquer S, Sebille V, Faye A, Djuranovic D, Raphael JC, Gajdos P, Bellisant E (2000) Compartmentalized inducible nitric-oxide synthase activity in septic shock. Lancet 355:1143–1148CrossRefPubMed

11.

Padgett EL, Pruett B (1995) Rat, mouse and human neutrophils stimulated by variety of activating agents produced much less nitrite than rodent macrophages. Immunology 84:125–141

12.

Miles AM, Owens MW, Milligan S, Johnson GG, Fields JZ, Ing TS, Kottapalli V, Keshavarzian A, Grisham MB (1995) Nitric oxide synthase in circulating versus extravasated polymorphonuclear leukocytes. J Leukoc Biol 58:616–622PubMed

13.

Yan L, Vandivier RW, Suffredini AF, Danner RL (1994) Human polymorphonuclear leukocytes lack detectable nitric oxide synthase activity. J Immunol 153:1825–1834PubMed

14.

Tsukahara Y, Morisaki T, Kojina M, Uchiyama M, Tanaka M (2001) iNOS expression by activated neutrophils from patients with sepsis. ANZ J Surg 71:15–20CrossRefPubMed

15.

Wheeler MA, Smith SD, Garcia-Cardena G, Nathan CF, Weiss RM, Sessa WC (1997) Bacterial infection induces nitric oxide synthase in human neutrophils. J Clin Invest 99:110–116PubMed

16.

Gomez-Jimenez J, Salgado A, Mourelle M, Martin MC, Segura RM, Peracaula R, Moncada S (1995) L-Arginine: nitric oxide pathway in endotoxemia and human septic shock. Crit Care Med 23:253–258CrossRefPubMed

17.

Sato K, Miyakawa K, Takeya M, Hattori R, Yui Y, Sunamoto M, Ichimoro Y, Ushio Y, Takahashi K (1995) Immunohistological expression of inducible nitric oxide synthase (iNOS) in reversible endotoxic shock studied by a novel monoclonal antibody against rat iNOS. J Leukoc Biol 57:36–44PubMed

Title: Differential inducible nitric oxide synthase activity in circulating neutrophils vs. mononuclears of septic shock patients
Authors: Moshe Hersch
Jeremy A. Scott
Gabriel Izbicki
David McCormack
Gedeminas Cepinkas
Marlies Ostermann
William J. Sibbald
Publication date: 01-08-2005
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 8/2005
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-005-2680-7

At a glance: The STEP trials

Springer Medicine

Differential inducible nitric oxide synthase activity in circulating neutrophils vs. mononuclears of septic shock patients

Abstract

Objective:

Design and setting:

Patients:

Measurements and results:

Conclusions:

At a glance: The STEP trials

Springer Medicine

Abstract

Objective:

Design and setting:

Patients:

Measurements and results:

Conclusions:

Please log in to get access to this content

Other articles of this Issue 8/2005

Safety and efficacy of colistin in Acinetobacter and Pseudomonas infections: a prospective cohort study

Successful long-term program for controlling methicillin-resistant Staphylococcus aureus in intensive care units

Does the brain become heavier or lighter after trauma? The long story of brain water content and its direct or indirect measurement

Antithrombin ameliorates endotoxin-induced organ dysfunction more efficiently when combined with danaparoid sodium than with unfractionated heparin

Hemodynamic variables related to outcome in septic shock

Prone positioning: do not turn it off!