Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Suramin inhibits macrophage activation by human group IIA phospholipase A(2), but does not affect bactericidal activity of the enzyme

Full text
Author(s):
Aragao, E. A. [1] ; Chioato, L. [2] ; Ferreira, T. L. [2] ; Medeiros, A. I. de [3] ; Secatto, A. [3] ; Faccioli, L. H. [3] ; Ward, R. J. [1]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, FFCLRP, Dept Chem, BR-05508 Sao Paulo - Brazil
[2] Univ Sao Paulo, FMRP, Dept Biochem & Immunol, BR-05508 Sao Paulo - Brazil
[3] Univ Sao Paulo, FCFRP, Dept Anal Clin Toxicol & Bromatol, BR-05508 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Inflammation Research; v. 58, n. 4, p. 210-217, APR 2009.
Web of Science Citations: 2
Abstract

Suramin is a polysulphonated napthylurea antiprotozoal and anthelminitic drug, which also presents inhibitory activity against a broad range of enzymes. Here we evaluate the effect of suramin on the hydrolytic and biological activities of secreted human group IIA phospholipase A(2) (hsPLA(2)GIIA). The hsPLA(2)GIIA was expressed in E. coli, and refolded from inclusion bodies. The hydrolytic activity of the recombinant enzyme was measured using mixed dioleoylphosphatidylcholine/dioleoylphosphatidylglycerol (DOPC/DOPG) liposomes. The activation of macrophage cell line RAW 264.7 by hsPLA(2) GIIA was monitored by NO release, and bactericidal activity against Micrococcus luteus was evaluated by colony counting and by flow cytometry using the fluorescent probe Sytox Green. The hydrolytic activity of the hsPLA(2) GIIA was inhibited by a concentration of 100 nM suramin and the activation of macrophages by hsPLA(2) GIIA was abolished at protein/suramin molar ratios where the hydrolytic activity of the enzyme was inhibited. In contrast, both the bactericidal activity of hsPLA(2) GIIA against Micrococcus luteus and permeabilization of the bacterial inner membrane were unaffected by suramin concentrations up to 50 mu M. These results demonstrate that suramin selectively inhibits the activity of the hsPLA(2) GIIA against macrophages, whilst leaving the anti-bacterial function unchanged. (AU)