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The effect of phosphodiesterase III inhibitors on human neutrophil function.
Crit Care Med. 2000 Apr; 28(4):1001-5.CC

Abstract

OBJECTIVES

Neutrophils play an important role in ridding the body of bacteria and cellular debris. Several neutrophil functions are thought to be regulated by inotropes that increase cellular levels of cyclic adenosine monophosphate, including phosphodiesterase (PDE) inhibitors. We have investigated the effect of amrinone, milrinone, and olprinone, type III PDE (PDE-III) inhibitors, on several human neutrophil functions.

DESIGN

Prospective in vitro study.

SETTING

Academic research laboratory.

SUBJECTS

Neutrophils isolated from 12 healthy adult volunteers.

INTERVENTIONS

We measured chemotaxis, phagocytosis, reactive oxygen species production, intracellular calcium ion concentration, and cyclic adenosine monophosphate levels in neutrophils in the absence and the presence (at clinically relevant concentrations, 10 times, and 100 times those concentrations) of amrinone, milrinone, or olprinone. We also measured reactive oxygen species production under the same condition in a xanthine-xanthine oxidase system

MEASUREMENTS AND MAIN RESULTS

None of the PDE-III inhibitors impaired neutrophil chemotaxis or phagocytosis. Amrinone at clinically relevant or higher concentrations and milrinone at high concentrations reduced superoxide, hydrogen peroxide, and hydroxyl radical levels in neutrophils and in the xanthine-xanthine oxidase system. Olprinone did not have those effects, and none of the PDE-III inhibitors had an effect on intracellular calcium ion concentration or cyclic adenosine monophosphate production in neutrophils stimulated by a chemotactic factor.

CONCLUSIONS

The ability of amrinone to scavenge reactive oxygen species at clinically relevant concentrations while not affecting neutrophil function suggests that the PDE inhibitor can be used without detriment in severely ill patients.

Authors+Show Affiliations

Department of Anaesthesiology, Kobe University School of Medicine, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10809273

Citation

Mikawa, K, et al. "The Effect of Phosphodiesterase III Inhibitors On Human Neutrophil Function." Critical Care Medicine, vol. 28, no. 4, 2000, pp. 1001-5.
Mikawa K, Akamatsu H, Nishina K, et al. The effect of phosphodiesterase III inhibitors on human neutrophil function. Crit Care Med. 2000;28(4):1001-5.
Mikawa, K., Akamatsu, H., Nishina, K., Shiga, M., Maekawa, N., Obara, H., & Niwa, Y. (2000). The effect of phosphodiesterase III inhibitors on human neutrophil function. Critical Care Medicine, 28(4), 1001-5.
Mikawa K, et al. The Effect of Phosphodiesterase III Inhibitors On Human Neutrophil Function. Crit Care Med. 2000;28(4):1001-5. PubMed PMID: 10809273.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of phosphodiesterase III inhibitors on human neutrophil function. AU - Mikawa,K, AU - Akamatsu,H, AU - Nishina,K, AU - Shiga,M, AU - Maekawa,N, AU - Obara,H, AU - Niwa,Y, PY - 2000/5/16/pubmed PY - 2000/6/8/medline PY - 2000/5/16/entrez SP - 1001 EP - 5 JF - Critical care medicine JO - Crit Care Med VL - 28 IS - 4 N2 - OBJECTIVES: Neutrophils play an important role in ridding the body of bacteria and cellular debris. Several neutrophil functions are thought to be regulated by inotropes that increase cellular levels of cyclic adenosine monophosphate, including phosphodiesterase (PDE) inhibitors. We have investigated the effect of amrinone, milrinone, and olprinone, type III PDE (PDE-III) inhibitors, on several human neutrophil functions. DESIGN: Prospective in vitro study. SETTING: Academic research laboratory. SUBJECTS: Neutrophils isolated from 12 healthy adult volunteers. INTERVENTIONS: We measured chemotaxis, phagocytosis, reactive oxygen species production, intracellular calcium ion concentration, and cyclic adenosine monophosphate levels in neutrophils in the absence and the presence (at clinically relevant concentrations, 10 times, and 100 times those concentrations) of amrinone, milrinone, or olprinone. We also measured reactive oxygen species production under the same condition in a xanthine-xanthine oxidase system MEASUREMENTS AND MAIN RESULTS: None of the PDE-III inhibitors impaired neutrophil chemotaxis or phagocytosis. Amrinone at clinically relevant or higher concentrations and milrinone at high concentrations reduced superoxide, hydrogen peroxide, and hydroxyl radical levels in neutrophils and in the xanthine-xanthine oxidase system. Olprinone did not have those effects, and none of the PDE-III inhibitors had an effect on intracellular calcium ion concentration or cyclic adenosine monophosphate production in neutrophils stimulated by a chemotactic factor. CONCLUSIONS: The ability of amrinone to scavenge reactive oxygen species at clinically relevant concentrations while not affecting neutrophil function suggests that the PDE inhibitor can be used without detriment in severely ill patients. SN - 0090-3493 UR - https://www.unboundmedicine.com/medline/citation/10809273/The_effect_of_phosphodiesterase_III_inhibitors_on_human_neutrophil_function_ L2 - https://dx.doi.org/10.1097/00003246-200004000-00015 DB - PRIME DP - Unbound Medicine ER -