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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Inflammation Research; v. 58, n. 4, p. 210-217, APR 2009.
• Citações Web of Science: 2

Resumo

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)

• Processo FAPESP: 01/00279-8 - Papel dos resíduos positivamente carregados nas funções farmacológicas de PLA2s de serpentes e sinovial humana
• Beneficiário: Lucimara Chioato
• Modalidade de apoio: Bolsas no Brasil - Doutorado