Chemokine CXCL1/KC and Its Receptor CXCR2 Are Responsible for Neutrophil Chemotaxis in Adenoviral Keratitis

Overview

Journal J Interferon Cytokine Res

Publisher Mary Ann Liebert

Specialty Allergy & Immunology

Date 2009 Aug 1

PMID 19642907

Citations 53

Authors

Ashish V Chintakuntlawar

James Chodosh

Affiliations

Soon will be listed here.

Abstract

Epidemic keratoconjunctivitis (EKC), caused by human adenovirus (HAdV), is one of the most common ocular infections and results in corneal inflammation and subepithelial infiltrates. Adenoviral keratitis causes significant morbidity to the patients, and is characterized by infiltration of leukocytes in the corneal stroma, and expression of chemokines. The exact role of these chemokines in adenoviral infection has not been studied due to lack of animal models. Here, we have characterized the role of chemokine CXCL1/KC and receptor CXCR2 in adenoviral keratitis using a novel mouse model. Analysis of chemokine expression, leukocyte infiltration, and development of keratitis was performed by ELISA, flow cytometry, and histopathology, respectively. Deficiency of CXCL1 and CXCR2 resulted in delayed infiltration of neutrophils, but not inflammatory monocytes in HAdV-37 corneal infection. CXCL1(-/-) mice showed decreased expression of CXCL2/MIP-2, but not CCL2/MCP-1. CXCR2(-/-) mice showed increased expression of CXCL1 and CXCL2, but not CCL2. Both CXCL1(-/-) and CXCR2(-/-) mice demonstrated keratitis similar to wild-type mice. In conclusion, both CXCL1 and CXCR2 play an important role in chemokine expression and neutrophil infiltration following adenoviral corneal infection, but have a redundant role in the development of keratitis.

Citing Articles

Type 2 diabetes is associated with increased circulating levels of 3-hydroxydecanoate activating GPR84 and neutrophil migration.

Mikkelsen R, Arora T, Trost K, Dmytriyeva O, Jensen S, Meijnikman A iScience. 2022; 25(12):105683.

PMID: 36561890 PMC: 9763857. DOI: 10.1016/j.isci.2022.105683.

Overriding impaired FPR chemotaxis signaling in diabetic neutrophil stimulates infection control in murine diabetic wound.

Roy R, Zayas J, Singh S, Delgado K, Wood S, Mohamed M Elife. 2022; 11.

PMID: 35112667 PMC: 8846594. DOI: 10.7554/eLife.72071.

Human Adenovirus Species D Interactions with Corneal Stromal Cells.

Rajaiya J, Saha A, Zhou X, Chodosh J Viruses. 2021; 13(12).

PMID: 34960773 PMC: 8709199. DOI: 10.3390/v13122505.

Role of Neutrophils on the Ocular Surface.

Mun Y, Hwang J, Shin Y Int J Mol Sci. 2021; 22(19).

PMID: 34638724 PMC: 8508808. DOI: 10.3390/ijms221910386.

A New Look at Vaccine Strategies Against PPRV Focused on Adenoviral Candidates.

Rojas J, Sevilla N, Martin V Front Vet Sci. 2021; 8:729879.

PMID: 34568477 PMC: 8455998. DOI: 10.3389/fvets.2021.729879.

References

Webster N, Crowe S . Matrix metalloproteinases, their production by monocytes and macrophages and their potential role in HIV-related diseases. J Leukoc Biol. 2006; 80(5):1052-66. DOI: 10.1189/jlb.0306152. View

Lu P, Li L, Mukaida N, Zhang X . Alkali-induced corneal neovascularization is independent of CXCR2-mediated neutrophil infiltration. Cornea. 2007; 26(2):199-206. DOI: 10.1097/01.ico.0000248385.16896.34. View

Alcorn M, Booth J, Coggeshall K, Metcalf J . Adenovirus type 7 induces interleukin-8 production via activation of extracellular regulated kinase 1/2. J Virol. 2001; 75(14):6450-9. PMC: 114368. DOI: 10.1128/JVI.75.14.6450-6459.2001. View

Xiao J, Chodosh J . JNK regulates MCP-1 expression in adenovirus type 19-infected human corneal fibroblasts. Invest Ophthalmol Vis Sci. 2005; 46(10):3777-82. DOI: 10.1167/iovs.05-0724. View

Van Damme J, Wuyts A, Froyen G, Van Coillie E, Struyf S, Billiau A . Granulocyte chemotactic protein-2 and related CXC chemokines: from gene regulation to receptor usage. J Leukoc Biol. 1997; 62(5):563-9. DOI: 10.1002/jlb.62.5.563. View

Bozic C, Kolakowski Jr L, Gerard N, Garcia-Rodriguez C, Conklyn M, Breslow R . Expression and biologic characterization of the murine chemokine KC. J Immunol. 1995; 154(11):6048-57. View

Yan X, Tumpey T, Kunkel S, Oakes J, Lausch R . Role of MIP-2 in neutrophil migration and tissue injury in the herpes simplex virus-1-infected cornea. Invest Ophthalmol Vis Sci. 1998; 39(10):1854-62. View

Montgomery R, Booth C, Wang X, Blaho V, Malawista S, Brown C . Recruitment of macrophages and polymorphonuclear leukocytes in Lyme carditis. Infect Immun. 2006; 75(2):613-20. PMC: 1828503. DOI: 10.1128/IAI.00685-06. View

Muller W . New mechanisms and pathways for monocyte recruitment. J Exp Med. 2001; 194(9):F47-51. PMC: 2195978. DOI: 10.1084/jem.194.9.f47. View

10.

Hestdal K, Ruscetti F, Ihle J, Jacobsen S, Dubois C, Kopp W . Characterization and regulation of RB6-8C5 antigen expression on murine bone marrow cells. J Immunol. 1991; 147(1):22-8. View

11.

Khan S, Cole N, Hume E, Garthwaite L, Conibear T, Miles D . The role of CXC chemokine receptor 2 in Pseudomonas aeruginosa corneal infection. J Leukoc Biol. 2006; 81(1):315-8. DOI: 10.1189/jlb.0506344. View

12.

Baggiolini M, Walz A, Kunkel S . Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989; 84(4):1045-9. PMC: 329758. DOI: 10.1172/JCI114265. View

13.

Banerjee K, Biswas P, Kim B, Lee S, Rouse B . CXCR2-/- mice show enhanced susceptibility to herpetic stromal keratitis: a role for IL-6-induced neovascularization. J Immunol. 2004; 172(2):1237-45. DOI: 10.4049/jimmunol.172.2.1237. View

14.

Baggiolini M, DEWALD B, Walz A . Activation of human neutrophils by NAP-1 and other chemotactic agonists. Adv Exp Med Biol. 1991; 305:11-21. DOI: 10.1007/978-1-4684-6009-4_2. View

15.

Kim B, Sarangi P, Lee Y, Kaistha S, Lee S, Rouse B . Depletion of MCP-1 increases development of herpetic stromal keratitis by innate immune modulation. J Leukoc Biol. 2006; 80(6):1405-15. DOI: 10.1189/jlb.0406295. View

16.

Gu L, Okada Y, Clinton S, Gerard C, Sukhova G, Libby P . Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell. 1998; 2(2):275-81. DOI: 10.1016/s1097-2765(00)80139-2. View

17.

Cole N, Bao S, Thakur A, Willcox M, Husband A . KC production in the cornea in response to Pseudomonas aeruginosa challenge. Immunol Cell Biol. 2000; 78(1):1-4. DOI: 10.1046/j.1440-1711.2000.00860.x. View

18.

Natarajan K, Rajala M, Chodosh J . Corneal IL-8 expression following adenovirus infection is mediated by c-Src activation in human corneal fibroblasts. J Immunol. 2003; 170(12):6234-43. DOI: 10.4049/jimmunol.170.12.6234. View

19.

Bae S, Jung Y, Woo S, Park M, Seoh J, Ryu K . Distinct locomotive patterns of granulocytes, monocytes and lymphocytes in a stable concentration gradient of chemokines. Int J Lab Hematol. 2008; 30(2):139-48. DOI: 10.1111/j.1751-553X.2007.00914.x. View

20.

Lin M, Carlson E, Diaconu E, Pearlman E . CXCL1/KC and CXCL5/LIX are selectively produced by corneal fibroblasts and mediate neutrophil infiltration to the corneal stroma in LPS keratitis. J Leukoc Biol. 2006; 81(3):786-92. PMC: 3909486. DOI: 10.1189/jlb.0806502. View