Leukotriene B4-loaded microspheres: a new therapeutic strategy to modulate cell activation.
BACKGROUND
Leukotriene B4 (LTB4) is a potent inflammatory mediator that also stimulates the immune response. In addition, it promotes polymorphonuclear leukocyte phagocytosis, chemotaxis, chemokinesis and modulates cytokines release. Regarding chemical instability of the leukotriene molecule, in the present study we assessed the immunomodulatory activities conferred by LTB4 released from microspheres (MS). A previous oil-in-water emulsion solvent extraction-evaporation method was chosen to prepare LTB4-loaded MS.


RESULTS
In the mice cremasteric microcirculation, intraescrotal injection of 0.1 ml of LTB4-loaded MS provoked significant increases in leukocyte rolling flux, adhesion and emigration besides significant decreases in the leukocyte rolling velocity. LTB4-loaded MS also increase peroxisome proliferator-activated receptor-alpha (PPARalpha) expression by murine peritoneal macrophages and stimulate them to generate nitrite levels. Monocyte chemoattractant protein-1 (MCP-1) and nitric oxide (NO) productions were also increased when human umbilical vein and artery endothelial cells (HUVECs and HUAECs, respectively) were stimulated with LTB4-loaded MS.


CONCLUSIONS
LTB4-loaded MS preserve the biological activity of the encapsulated mediator indicating their use as a new strategy to modulate cell activation, especially in the innate immune response.
Nicolete
Roberto
R
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av, do Café s/n, 14040-903, Ribeirão Preto, São Paulo, Brasil. nicolete@fcfrp.usp.br; Cristina Rius
Rius
Cristina
C
Piqueras
Laura
L
Jose
Peter J
PJ
Sorgi
Carlos A
CA
Soares
Edson G
EG
Sanz
Maria J
MJ
Faccioli
Lúcia H
LH
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000096:biosynthesis; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000276:immunology*; D007975:Leukotriene B4 / Q000008:administration & dosage / Q000276:immunology*; D008168:Lung / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008863:Microspheres; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites; D047493:PPAR alpha / Q000378:metabolism
D018932:Chemokine CCL2; D009573:Nitrites; D047493:PPAR alpha; D007975:Leukotriene B4; D009569:Nitric Oxide