PMID- 18627613 OWN - NLM STAT- MEDLINE DCOM- 20080903 LR - 20211020 IS - 1471-2172 (Electronic) IS - 1471-2172 (Linking) VI - 9 DP - 2008 Jul 15 TI - Leukotriene B4-loaded microspheres: a new therapeutic strategy to modulate cell activation. PG - 36 LID - 10.1186/1471-2172-9-36 [doi] AB - 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. CONCLUSION: 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. FAU - Nicolete, Roberto AU - Nicolete R AD - Departamento de Analises Clinicas, Toxicologicas e Bromatologicas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av, do Cafe s/n, 14040-903, Ribeirao Preto, Sao Paulo, Brasil. nicolete@fcfrp.usp.br; Cristina Rius FAU - Rius, Cristina AU - Rius C FAU - Piqueras, Laura AU - Piqueras L FAU - Jose, Peter J AU - Jose PJ FAU - Sorgi, Carlos A AU - Sorgi CA FAU - Soares, Edson G AU - Soares EG FAU - Sanz, Maria J AU - Sanz MJ FAU - Faccioli, Lucia H AU - Faccioli LH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080715 PL - England TA - BMC Immunol JT - BMC immunology JID - 100966980 RN - 0 (Chemokine CCL2) RN - 0 (Nitrites) RN - 0 (PPAR alpha) RN - 1HGW4DR56D (Leukotriene B4) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Animals MH - Cell Adhesion MH - Cell Movement MH - Chemokine CCL2/biosynthesis MH - Endothelial Cells/*immunology/metabolism MH - Humans MH - Leukocyte Rolling MH - Leukocytes/*immunology MH - Leukotriene B4/administration & dosage/*immunology MH - Lung/immunology MH - Macrophages, Peritoneal/*immunology/metabolism MH - Mice MH - Microspheres MH - Nitric Oxide/metabolism MH - Nitrites MH - PPAR alpha/metabolism PMC - PMC2483258 EDAT- 2008/07/17 09:00 MHDA- 2008/09/04 09:00 PMCR- 2008/07/15 CRDT- 2008/07/17 09:00 PHST- 2008/03/19 00:00 [received] PHST- 2008/07/15 00:00 [accepted] PHST- 2008/07/17 09:00 [pubmed] PHST- 2008/09/04 09:00 [medline] PHST- 2008/07/17 09:00 [entrez] PHST- 2008/07/15 00:00 [pmc-release] AID - 1471-2172-9-36 [pii] AID - 10.1186/1471-2172-9-36 [doi] PST - epublish SO - BMC Immunol. 2008 Jul 15;9:36. doi: 10.1186/1471-2172-9-36.