PMID- 11937571 OWN - NLM STAT- MEDLINE DCOM- 20020523 LR - 20190515 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 168 IP - 8 DP - 2002 Apr 15 TI - Monocyte chemoattractant protein-1 and 5-lipoxygenase products recruit leukocytes in response to platelet-activating factor-like lipids in oxidized low-density lipoprotein. PG - 4112-20 AB - Oxidized low-density lipoprotein (LDL) contains inflammatory agents, including oxidatively fragmented phospholipids that activate the platelet-activating factor (PAF) receptor, but in vivo events caused by these pathologically generated agents are not well defined. Injection of PAF-like lipids derived from oxidized LDL, or C(4)-PAF that is a major PAF-like lipid in these particles, into the pleural cavity of mice resulted in rapid monocyte, neutrophil, and eosinophil accumulation. Increased numbers of intracellular lipid bodies in these cells show they were in an inflammatory environment. Leukocyte recruitment was abolished by a PAF receptor antagonist, as expected. PAF-like lipids induced 5-lipoxygenase expression in leukocytes, mRNA expression for monocyte chemoattractant protein-1 (MCP-1) and other chemokines, synthesis of MCP-1, and leukotriene B(4). The 5-lipoxygenase inhibitor zileuton impaired neutrophil influx, while MCP-1 had a more global role, as determined with MCP-1(-/-) mice. The lack of MCP-1 abrogated leukocyte accumulation and lipid body formation both in vivo and in vitro and chemokine transcription in vivo, and reduced in vivo leukotriene B(4) production. Thus, PAF-like phospholipids in oxidized LDL induce an inflammatory infiltrate through the PAF receptor, chemokine transcription, lipid body formation, and 5-lipoxygenase expression in leukocytes. MCP-1 has a key role in this inflammatory response, and 5-lipoxygenase products are essential for neutrophil recruitment into the inflamed pleural cavity. FAU - Silva, Adriana R AU - Silva AR AD - Departamento de Fisiologia e Farmacodinamica, Instituto Oswaldo Cruz, Fundacao Oswaldo Cruz, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. FAU - de Assis, Edson F AU - de Assis EF FAU - Caiado, Lara F C AU - Caiado LF FAU - Marathe, Gopal K AU - Marathe GK FAU - Bozza, Marcelo T AU - Bozza MT FAU - McIntyre, Thomas M AU - McIntyre TM FAU - Zimmerman, Guy A AU - Zimmerman GA FAU - Prescott, Stephen M AU - Prescott SM FAU - Bozza, Patricia T AU - Bozza PT FAU - Castro-Faria-Neto, Hugo C AU - Castro-Faria-Neto HC LA - eng GR - HL44252/HL/NHLBI NIH HHS/United States GR - HL44513/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Chemokine CCL2) RN - 0 (Chemokines) RN - 0 (Diterpenes) RN - 0 (Ginkgolides) RN - 0 (Lactones) RN - 0 (Lipoproteins, LDL) RN - 0 (Phospholipids) RN - 0 (Platelet Activating Factor) RN - 0 (RNA, Messenger) RN - 0 (oxidized low density lipoprotein) RN - DF149B9460 (ginkgolide B) RN - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase) SB - IM MH - Animals MH - Arachidonate 5-Lipoxygenase/biosynthesis/*physiology MH - Cell Movement/genetics/*immunology MH - Chemokine CCL2/biosynthesis/deficiency/genetics/*physiology MH - Chemokines/biosynthesis/genetics MH - Disease Models, Animal MH - *Diterpenes MH - Eosinophils/immunology/metabolism/pathology MH - Ginkgolides MH - Humans MH - Inflammation/enzymology/metabolism/pathology MH - Lactones/pharmacology MH - Leukocytes/*enzymology/*immunology/pathology MH - Lipoproteins, LDL/metabolism/*physiology MH - Mice MH - Neutrophils/immunology/metabolism/pathology MH - Phospholipids/isolation & purification/metabolism/*physiology MH - Platelet Activating Factor/antagonists & inhibitors/*physiology MH - Pleural Effusion/metabolism/pathology MH - Pleurisy/enzymology/immunology/metabolism/pathology MH - RNA, Messenger/biosynthesis EDAT- 2002/04/09 10:00 MHDA- 2002/05/25 10:01 CRDT- 2002/04/09 10:00 PHST- 2002/04/09 10:00 [pubmed] PHST- 2002/05/25 10:01 [medline] PHST- 2002/04/09 10:00 [entrez] AID - 10.4049/jimmunol.168.8.4112 [doi] PST - ppublish SO - J Immunol. 2002 Apr 15;168(8):4112-20. doi: 10.4049/jimmunol.168.8.4112.