Modulation of infection-mediated migration of neutrophils and CXCR2 trafficking by osteopontin.

Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 0374672 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2567 (Electronic) Linking ISSN: 00192805 NLM ISO Abbreviation: Immunology Subsets: MEDLINE

Original Publication: Oxford : Blackwell Scientific Publications

Bacterial Infections/*immunology ; Integrin alpha5/*metabolism ; Neutrophils/*immunology ; Osteopontin/*metabolism ; Pulpitis/*immunology; Animals ; Bacterial Load ; Cell Movement ; Chemokine CXCL1/metabolism ; Disease Models, Animal ; Humans ; Immunity, Innate/genetics ; Integrin alpha5/genetics ; Male ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Osteopontin/genetics ; Receptors, Interleukin-8B/metabolism

Osteopontin (OPN) is a pro-inflammatory protein that paradoxically protects against inflammation and bone destruction in a mouse model of endodontic infection. Here we have tested the hypothesis that this effect of OPN is mediated by effects on migration of innate immune cells to the site of infection. Using the air pouch as a model of endodontic infection in mice, we showed that neutrophil accumulation at the site of infection with a mixture of endodontic pathogens is significantly reduced in OPN-deficient mice. Reduced neutrophil accumulation in the absence of OPN was accompanied by an increase in bacterial load. OPN-deficiency did not affect neutrophil survival, CXCR2 ligand expression, or the production of inflammatory cytokines in the air pouch. In vitro, OPN enhanced neutrophil migration to CXCL1, whereas in vivo, inhibition of CXCR2 suppressed cellular infiltration in air pouches of infected wild-type mice by > 50%, but had no effect in OPN-deficient mice. OPN increased cell surface expression of CXCR2 on bone marrow neutrophils in an integrin-α v -dependent manner, and suppressed the internalization of CXCR2 in the absence of ligand. Together, these results support a model where the protective effect of OPN results from enhanced initial neutrophil accumulation at sites of infection resulting in optimal bacterial killing. We describe a novel mechanism for this effect of OPN: integrin-α v -dependent suppression of CXCR2 internalization in neutrophils, which increases the ability of these cells to migrate to sites of infection in response to CXCR2 ligands.
(© 2016 John Wiley & Sons Ltd.)

J Cell Biol. 2008 Oct 6;183(1):143-55. (PMID: 18838556)
J Infect Dis. 2011 Jun 15;203(12):1850-8. (PMID: 21606543)
Am J Physiol Lung Cell Mol Physiol. 2013 Jul 15;305(2):L118-29. (PMID: 23666750)
Infect Immun. 2010 Jun;78(6):2620-30. (PMID: 20368349)
Biochem Biophys Res Commun. 1998 Sep 18;250(2):287-92. (PMID: 9753622)
Front Immunol. 2012 Aug 02;3:242. (PMID: 22876249)
J Immunol. 2000 Oct 1;165(7):3626-30. (PMID: 11034365)
J Immunol. 2004 Aug 1;173(3):2084-90. (PMID: 15265944)
Biochem Biophys Res Commun. 2004 Jun 25;319(2):576-81. (PMID: 15178445)
J Leukoc Biol. 2007 Jan;81(1):315-8. (PMID: 17028201)
J Biol Chem. 1999 Dec 17;274(51):36328-34. (PMID: 10593924)
J Dent Res. 2009 Nov;88(11):969-81. (PMID: 19828883)
J Bone Miner Res. 1998 Jul;13(7):1101-11. (PMID: 9661074)
J Biol Chem. 1995 Apr 28;270(17):9917-25. (PMID: 7537271)
Crit Care. 2015 Feb 26;19:53. (PMID: 25887405)
Proc Natl Acad Sci U S A. 2012 Jun 26;109 (26):10480-5. (PMID: 22699511)
Pharmacol Ther. 2006 Oct;112(1):139-49. (PMID: 16720046)
Infect Immun. 2014 Oct;82(10):4068-79. (PMID: 25024367)
J Biol Chem. 2002 Mar 15;277(11):9175-82. (PMID: 11741994)
J Biol Chem. 1998 Apr 24;273(17):10095-8. (PMID: 9553055)
J Cell Sci. 2015 Mar 1;128(5):839-52. (PMID: 25663697)
J Vis Exp. 2013 Jul 10;(77):e50586. (PMID: 23892876)
Crit Rev Immunol. 2006;26(4):307-16. (PMID: 17073556)
Toxicol Appl Pharmacol. 2005 Aug 22;207(1):25-38. (PMID: 15885730)
Immunology. 2010 Jan;129(1):105-14. (PMID: 19824920)
J Immunol. 2012 Sep 15;189(6):2824-32. (PMID: 22869904)
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002 Dec;94(6):651-2. (PMID: 12464886)
Curr Opin Cell Biol. 2013 Oct;25(5):627-32. (PMID: 23797030)
J Cell Biol. 1999 Apr 19;145(2):413-20. (PMID: 10209034)
Clin Diagn Lab Immunol. 2004 Jan;11(1):106-10. (PMID: 14715554)
Arthritis Rheum. 2009 Oct;60(10):2902-12. (PMID: 19790060)
Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15823-8. (PMID: 17895374)
J Cell Biochem. 2007 Nov 1;102(4):925-35. (PMID: 17786932)
J Immunol. 2013 Aug 15;191(4):1785-91. (PMID: 23863904)
J Pathol. 2006 Mar;208(4):473-85. (PMID: 16440289)
Matrix Biol. 2015 Jan;41:19-25. (PMID: 25446551)
Curr Opin Cell Biol. 2014 Apr;27:72-7. (PMID: 24680433)
Immunology. 1999 May;97(1):117-23. (PMID: 10447722)
Dis Model Mech. 2013 Jan;6(1):197-205. (PMID: 22917925)
Nat Rev Rheumatol. 2014 Oct;10(10):593-601. (PMID: 24914698)
J Immunol. 2014 Mar 1;192(5):2186-94. (PMID: 24510965)
J Dent Res. 2015 Dec;94(12 ):1638-45. (PMID: 26341976)
PLoS One. 2015 Jul 14;10(7):e0132752. (PMID: 26171605)
Pathol Int. 2011 May;61(5):265-80. (PMID: 21501293)
Immunology. 2007 Dec;122(4):466-75. (PMID: 17680800)
J Biol Chem. 2009 May 29;284(22):14769-76. (PMID: 19346516)
Methods Mol Biol. 2003;225:181-9. (PMID: 12769487)
Nat Immunol. 2013 Sep;14 (9):949-58. (PMID: 23933892)
Infect Immun. 2001 Feb;69(2):744-50. (PMID: 11159963)
J Cell Biochem. 2013 May;114(5):1194-202. (PMID: 23192608)
Expert Rev Mol Med. 2011 Apr 26;13:e15. (PMID: 21545755)
Clin Exp Metastasis. 2003;20(2):111-20. (PMID: 12705632)
Blood. 2008 Aug 15;112(4):935-45. (PMID: 18684880)
Virulence. 2015;6(3):216-22. (PMID: 25654162)
Blood. 2007 May 1;109(9):3794-802. (PMID: 17202320)
Eur Respir J. 2010 Dec;36(6):1337-45. (PMID: 20378602)

R01 DE022380 United States DE NIDCR NIH HHS

Keywords: CXCR2; endodontic infection; integrin-αv; osteopontin; receptor recycling

0 (Chemokine CXCL1)
0 (Integrin alpha5)
0 (Receptors, Interleukin-8B)
106441-73-0 (Osteopontin)

Date Created: 20160907 Date Completed: 20170523 Latest Revision: 20181113

20250114

PMC5341506

10.1111/imm.12668

27599164