Short-Term Regulation of Fc γ R-Mediated Phagocytosis by TLRs in Macrophages: Participation of 5-Lipoxygenase Products.

Publisher: Wiley Country of Publication: United States NLM ID: 9209001 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1466-1861 (Electronic) Linking ISSN: 09629351 NLM ISO Abbreviation: Mediators Inflamm Subsets: MEDLINE

Publication: 2023- : Hoboken, NJ : Wiley
Original Publication: Oxford, UK : Rapid Communications of Oxford Ltd., c1992-

Arachidonate 5-Lipoxygenase/*metabolism ; Erythrocytes/*drug effects ; Erythrocytes/*metabolism; Animals ; Arachidonate 5-Lipoxygenase/genetics ; Flavonoids/pharmacology ; Immunoblotting ; Leukotrienes/metabolism ; Macrophages, Alveolar/metabolism ; Male ; Mice ; Mice, Knockout ; Phagocytosis/drug effects ; Phagocytosis/genetics ; Phagocytosis/physiology ; Phosphorylation/drug effects ; Phosphorylation/genetics ; Rats ; Rats, Wistar ; Sheep ; Toll-Like Receptor 2/genetics ; Toll-Like Receptor 2/metabolism ; Toll-Like Receptor 3/genetics ; Toll-Like Receptor 3/metabolism ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 4/metabolism

TLRs recognize a broad spectrum of microorganism molecules, triggering a variety of cellular responses. Among them, phagocytosis is a critical process for host defense. Leukotrienes (LTs), lipid mediators produced from 5-lipoxygenase (5-LO) enzyme, increase Fc γ R-mediated phagocytosis. Here, we evaluated the participation of TLR2, TLR3, TLR4, and TLR9 in Fc γ R-mediated phagocytosis and whether this process is modulated by LTs. Rat alveolar macrophages (AMs), murine bone marrow-derived macrophages (BMDMs), and peritoneal macrophages (PMs) treated with TLR2, TLR3, and TLR4 agonists, but not TLR9, enhanced IgG-opsonized sheep red blood cell (IgG-sRBC) phagocytosis. Pretreatment of AMs or BMDMs with drugs that block LT synthesis impaired the phagocytosis promoted by TLR ligands, and TLR potentiation was also abrogated in PMs and BMDMs from 5-LO ^-/- mice. LTB 4 production induced by IgG engagement was amplified by TLR ligands, while cys-LTs were amplified by activation of TLR2 and TLR4, but not by TLR3. We also noted higher ERK1/2 phosphorylation in IgG-RBC-challenged cells when preincubated with TLR agonists. Furthermore, ERK1/2 inhibition by PD98059 reduced the phagocytic activity evoked by TLR agonists. Together, these data indicate that TLR2, TLR3, and TLR4 ligands, but not TLR9, amplify IgG-mediated phagocytosis by a mechanism which requires LT production and ERK-1/2 pathway activation.

Blood. 2003 Sep 1;102(5):1877-83. (PMID: 12730109)
J Cell Physiol. 2010 Mar;222(3):658-68. (PMID: 20020500)
J Clin Invest. 2011 Feb;121(2):671-82. (PMID: 21206089)
Br J Pharmacol. 2001 Dec;134(8):1619-28. (PMID: 11739237)
N Engl J Med. 2007 Nov 1;357(18):1841-54. (PMID: 17978293)
Cytokine. 2015 Aug;74(2):181-9. (PMID: 25846205)
FASEB J. 2010 Feb;24(2):637-47. (PMID: 19843712)
Blood. 2000 Apr 1;95(7):2407-12. (PMID: 10733514)
J Pharmacol Exp Ther. 1994 Nov;271(2):615-23. (PMID: 7965776)
J Immunol. 2007 Dec 15;179(12 ):8350-6. (PMID: 18056380)
Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8792-7. (PMID: 16720699)
J Med Microbiol. 2004 Dec;53(Pt 12):1187-93. (PMID: 15585496)
Clin Microbiol Rev. 2011 Jul;24(3):490-7. (PMID: 21734245)
Mol Immunol. 2009 Mar;46(6):1204-11. (PMID: 19223078)
Biochem Biophys Res Commun. 2005 Dec 9;338(1):102-10. (PMID: 16122704)
Nature. 1999 Oct 21;401(6755):811-5. (PMID: 10548109)
Eur J Pharmacol. 2007 Apr 30;561(1-3):214-9. (PMID: 17306251)
J Immunol. 2009 Jun 15;182(12):7690-7. (PMID: 19494293)
Science. 2003 Aug 1;301(5633):640-3. (PMID: 12855817)
Am J Physiol Lung Cell Mol Physiol. 2004 May;286(5):L921-30. (PMID: 15064239)
J Leukoc Biol. 2009 Apr;85(4):595-605. (PMID: 19112093)
J Immunol. 2012 Feb 1;188(3):1098-107. (PMID: 22198949)
Nat Immunol. 2003 Nov;4(11):1144-50. (PMID: 14556004)
Nature. 2009 Apr 30;458(7242):1191-5. (PMID: 19252480)
Annu Rev Immunol. 2015;33:393-416. (PMID: 25622194)
Annu Rev Immunol. 1999;17:593-623. (PMID: 10358769)
J Exp Med. 2004 Jan 5;199(1):81-90. (PMID: 14699082)
J Pediatr Surg. 2007 Jun;42(6):927-32; discussion 933. (PMID: 17560196)
J Orthop Res. 2011 Jul;29(7):984-92. (PMID: 21308757)
PLoS One. 2014 May 09;9(5):e96903. (PMID: 24816777)
Curr Drug Targets Inflamm Allergy. 2002 Mar;1(1):23-44. (PMID: 14561204)
Infect Immun. 2015 Jun;83(6):2242-54. (PMID: 25776754)
J Exp Med. 1997 Oct 6;186(7):1027-39. (PMID: 9314552)
Curr Opin Immunol. 2002 Feb;14(1):136-45. (PMID: 11790544)
Cytokine. 2011 Jul;55(1):40-7. (PMID: 21474333)
J Cell Biol. 1996 Dec;135(5):1249-60. (PMID: 8947549)
Cell Physiol Biochem. 2010;26(3):319-26. (PMID: 20798516)
Cell. 2007 Sep 21;130(6):1071-82. (PMID: 17889651)
J Immunol. 1996 Dec 15;157(12):5221-4. (PMID: 8955165)
Nature. 1994 Nov 10;372(6502):179-82. (PMID: 7969451)
J Immunol. 2000 Aug 15;165(4):2124-33. (PMID: 10925298)
Nat Immunol. 2001 Aug;2(8):675-80. (PMID: 11477402)
Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):E4110-8. (PMID: 25225402)
Trends Mol Med. 2007 Nov;13(11):460-9. (PMID: 18029230)
J Allergy Clin Immunol. 2010 May;125(5):985-92. (PMID: 20392481)
PLoS One. 2015 Aug 28;10(8):e0136947. (PMID: 26317438)

0 (Flavonoids)
0 (Leukotrienes)
0 (TLR3 protein, mouse)
0 (Tlr2 protein, mouse)
0 (Toll-Like Receptor 2)
0 (Toll-Like Receptor 3)
0 (Toll-Like Receptor 4)
EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)

Date Created: 20170913 Date Completed: 20180521 Latest Revision: 20181113

20250114

PMC5574301

10.1155/2017/2086840

28894350