Neutrophil effector functions triggered by Fc-gamma and/or complement receptors are dependent on B-ring hydroxylation pattern and physicochemical properties of flavonols.
Tissue damage in autoimmune diseases involves excessive production of reactive oxygen species (ROS) triggered by immune complexes (IC) and neutrophil (PMN) interactions via receptors for the Fc portion of IgG (FcgammaR) and complement receptors (CR). Modulation of both the effector potential of these receptors and ROS generation may be relevant to the maintenance of body homeostasis. In the present study, the modulatory effect of four flavonols (myricetin, quercetin, kaempferol, galangin) on rabbit PMN oxidative metabolism, specifically stimulated via FcgammaR, CR or both classes of receptors, was evaluated by luminol- and lucigenin-dependent chemiluminescence assays. Results showed that flavonol inhibitory effect was not dependent on the cell membrane receptor class stimulated but related to the lipophilicity of the compounds (their apparent partition coefficient values were obtained by high-performance liquid chromatography), and was also inversely related to the number of hydroxyl groups in the flavonol B ring and the ROS-scavenger activity (assessed by the luminol--H2O2--horseradish peroxidase reaction). Under the experimental conditions the flavonols tested were not toxic to PMNs (evaluated by lactate dehydrogenase release and trypan blue exclusion) and did not interfere with IC-induced phagocytosis (evaluated by transmission electron microscopy). Our results suggested that inhibition of IC-stimulated PMNs effector functions by the flavonols tested herein was the result of cooperation of different cellular mechanisms.
Moreira
Mirian R
MR
Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café s/n, Monte Alegre, Ribeirão Preto, SP 14040-903, Brazil.
Kanashiro
Alexandre
A
Kabeya
Luciana M
LM
Polizello
Ana Cristina M
AC
Azzolini
Ana Elisa C S
AE
Curti
Carlos
C
Oliveira
Carlos A
CA
T-do Amaral
Antonia
A
Lucisano-Valim
Yara M
YM
D000166:Acridines / Q000737:chemistry; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D001555:Benzene Derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003165:Complement System Proteins / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D044948:Flavonols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D006900:Hydroxylation; D007105:Immune Complex Diseases / Q000188:drug therapy / Q000378:metabolism; D007155:Immunologic Factors / Q000737:chemistry* / Q000378:metabolism; D044949:Kaempferols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008163:Luminescent Measurements; D008165:Luminol / Q000737:chemistry; D015394:Molecular Structure; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011794:Quercetin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D011951:Receptors, Complement / Q000276:immunology / Q000378:metabolism*; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000166:Acridines; D000936:Antigen-Antibody Complex; D001555:Benzene Derivatives; D005419:Flavonoids; D044948:Flavonols; D016166:Free Radical Scavengers; D007155:Immunologic Factors; D044949:Kaempferols; D011951:Receptors, Complement; D011961:Receptors, Fc; C037032:galangin; C033472:10,10'-dimethyl-9,9'-biacridinium; D008165:Luminol; C006552:kaempferol; C040015:myricetin; D003165:Complement System Proteins; D011794:Quercetin