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. 1996 Feb;70(2):1277–1281. doi: 10.1128/jvi.70.2.1277-1281.1996

Protective antibody therapy is associated with reduced chemokine transcripts in herpes simplex virus type 1 corneal infection.

Y H Su 1, X T Yan 1, J E Oakes 1, R N Lausch 1
PMCID: PMC189943  PMID: 8551595

Abstract

Herpes simplex virus type 1 (HSV-1) infection on the murine cornea induces an intense inflammatory response which can lead to blindness. This disease, known as herpes stromal keratitis, can be prevented by the timely passive transfer of monoclonal antibody specific for viral glycoprotein D (gD). Precisely how antibody treatment prevents excessive corneal inflammation is not known. In this study we investigated whether chemokine mRNA expression is inhibited by antibody treatment. Total cellular RNAs isolated from normal corneas and at various times after virus infection were analyzed via reverse transcription-PCR for mRNA coding for seven different chemokines. Constitutive levels of IP-10, KC, MIP-2, MCP-1, MIP-1 beta, and RANTES mRNA were detected in uninfected corneas of BALB/c mice. When the cornea was mechanically traumatized, message for all six chemokines was transiently elevated above constitutive levels. In contrast, HSV-1 infection resulted in prolonged enhanced chemokine message expression. The kinetics of mRNA accumulation was distinctive for each chemokine analyzed. MIP-1 alpha message, not detected constitutively, was not evident until day 7 postinfection. Administration of anti-HSV gD monoclonal antibody 1 day after infection was associated with reduced message for MIP-2, MCP-1, MIP-1 alpha, and MIP-1 beta. IP-10, KC, and RANTES messages were not altered. Collectively, our results suggest that anti-gD treatment may protect, at least in part, by inhibiting production of chemokines believed to promote inflammation.

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Selected References

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  1. Bevilacqua M. P. Endothelial-leukocyte adhesion molecules. Annu Rev Immunol. 1993;11:767–804. doi: 10.1146/annurev.iy.11.040193.004003. [DOI] [PubMed] [Google Scholar]
  2. Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [PubMed] [Google Scholar]
  3. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  4. Cochran B. H., Reffel A. C., Stiles C. D. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell. 1983 Jul;33(3):939–947. doi: 10.1016/0092-8674(83)90037-5. [DOI] [PubMed] [Google Scholar]
  5. Cubitt C. L., Tang Q., Monteiro C. A., Lausch R. N., Oakes J. E. IL-8 gene expression in cultures of human corneal epithelial cells and keratocytes. Invest Ophthalmol Vis Sci. 1993 Oct;34(11):3199–3206. [PubMed] [Google Scholar]
  6. Danoff T. M., Lalley P. A., Chang Y. S., Heeger P. S., Neilson E. G. Cloning, genomic organization, and chromosomal localization of the Scya5 gene encoding the murine chemokine RANTES. J Immunol. 1994 Feb 1;152(3):1182–1189. [PubMed] [Google Scholar]
  7. Hendricks R. L., Tao M. S., Glorioso J. C. Alterations in the antigenic structure of two major HSV-1 glycoproteins, gC and gB, influence immune regulation and susceptibility to murine herpes keratitis. J Immunol. 1989 Jan 1;142(1):263–269. [PubMed] [Google Scholar]
  8. Jones M. L., Mulligan M. S., Flory C. M., Ward P. A., Warren J. S. Potential role of monocyte chemoattractant protein 1/JE in monocyte/macrophage-dependent IgA immune complex alveolitis in the rat. J Immunol. 1992 Sep 15;149(6):2147–2154. [PubMed] [Google Scholar]
  9. Jones M. L., Warren J. S. Monocyte chemoattractant protein 1 in a rat model of pulmonary granulomatosis. Lab Invest. 1992 Apr;66(4):498–503. [PubMed] [Google Scholar]
  10. Kaplan G., Luster A. D., Hancock G., Cohn Z. A. The expression of a gamma interferon-induced protein (IP-10) in delayed immune responses in human skin. J Exp Med. 1987 Oct 1;166(4):1098–1108. doi: 10.1084/jem.166.4.1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kelner G. S., Kennedy J., Bacon K. B., Kleyensteuber S., Largaespada D. A., Jenkins N. A., Copeland N. G., Bazan J. F., Moore K. W., Schall T. J. Lymphotactin: a cytokine that represents a new class of chemokine. Science. 1994 Nov 25;266(5189):1395–1399. doi: 10.1126/science.7973732. [DOI] [PubMed] [Google Scholar]
  12. Koch A. E., Kunkel S. L., Harlow L. A., Johnson B., Evanoff H. L., Haines G. K., Burdick M. D., Pope R. M., Strieter R. M. Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis. J Clin Invest. 1992 Sep;90(3):772–779. doi: 10.1172/JCI115950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lasky L. A. Chemokines: combinatorial mediators of inflammation? Curr Biol. 1993 Jun 1;3(6):366–368. doi: 10.1016/0960-9822(93)90203-z. [DOI] [PubMed] [Google Scholar]
  14. Lausch R. N., Kleinschradt W. R., Monteiro C., Kayes S. G., Oakes J. E. Resolution of HSV corneal infection in the absence of delayed-type hypersensitivity. Invest Ophthalmol Vis Sci. 1985 Nov;26(11):1509–1515. [PubMed] [Google Scholar]
  15. Lausch R. N., Oakes J. E., Metcalf J. F., Scimeca J. M., Smith L. A., Robertson S. M. Quantitation of purified monoclonal antibody needed to prevent HSV-1 induced stromal keratitis in mice. Curr Eye Res. 1989 May;8(5):499–506. doi: 10.3109/02713688909000030. [DOI] [PubMed] [Google Scholar]
  16. Lausch R. N., Staats H., Metcalf J. F., Oakes J. E. Effective antibody therapy in herpes simplex virus ocular infection. Characterization of recipient immune response. Intervirology. 1990;31(2-4):159–165. doi: 10.1159/000150150. [DOI] [PubMed] [Google Scholar]
  17. Lousch R. N., Staats H., Oakes J. E., Cohen G. H., Eisenberg R. J. Prevention of herpes keratitis by monoclonal antibodies specific for discontinuous and continuous epitopes on glycoprotein D. Invest Ophthalmol Vis Sci. 1991 Sep;32(10):2735–2740. [PubMed] [Google Scholar]
  18. Lukacs N. W., Kunkel S. L., Strieter R. M., Warmington K., Chensue S. W. The role of macrophage inflammatory protein 1 alpha in Schistosoma mansoni egg-induced granulomatous inflammation. J Exp Med. 1993 Jun 1;177(6):1551–1559. doi: 10.1084/jem.177.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Metcalf J. F., Hamilton D. S., Reichert R. W. Herpetic keratitis in athymic (nude) mice. Infect Immun. 1979 Dec;26(3):1164–1171. doi: 10.1128/iai.26.3.1164-1171.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Metcalf J. F., Koga J., Chatterjee S., Whitley R. J. Passive immunization with monoclonal antibodies against herpes simplex virus glycoproteins protects mice against herpetic ocular disease. Curr Eye Res. 1987 Jan;6(1):173–177. doi: 10.3109/02713688709020086. [DOI] [PubMed] [Google Scholar]
  21. Miller M. D., Krangel M. S. Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit Rev Immunol. 1992;12(1-2):17–46. [PubMed] [Google Scholar]
  22. Newell C. K., Martin S., Sendele D., Mercadal C. M., Rouse B. T. Herpes simplex virus-induced stromal keratitis: role of T-lymphocyte subsets in immunopathology. J Virol. 1989 Feb;63(2):769–775. doi: 10.1128/jvi.63.2.769-775.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Oakes J. E., Monteiro C. A., Cubitt C. L., Lausch R. N. Induction of interleukin-8 gene expression is associated with herpes simplex virus infection of human corneal keratocytes but not human corneal epithelial cells. J Virol. 1993 Aug;67(8):4777–4784. doi: 10.1128/jvi.67.8.4777-4784.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ohmori Y., Hamilton T. A. A macrophage LPS-inducible early gene encodes the murine homologue of IP-10. Biochem Biophys Res Commun. 1990 May 16;168(3):1261–1267. doi: 10.1016/0006-291x(90)91164-n. [DOI] [PubMed] [Google Scholar]
  25. Oppenheim J. J., Zachariae C. O., Mukaida N., Matsushima K. Properties of the novel proinflammatory supergene "intercrine" cytokine family. Annu Rev Immunol. 1991;9:617–648. doi: 10.1146/annurev.iy.09.040191.003153. [DOI] [PubMed] [Google Scholar]
  26. Oquendo P., Alberta J., Wen D. Z., Graycar J. L., Derynck R., Stiles C. D. The platelet-derived growth factor-inducible KC gene encodes a secretory protein related to platelet alpha-granule proteins. J Biol Chem. 1989 Mar 5;264(7):4133–4137. [PubMed] [Google Scholar]
  27. Ransohoff R. M., Hamilton T. A., Tani M., Stoler M. H., Shick H. E., Major J. A., Estes M. L., Thomas D. M., Tuohy V. K. Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental autoimmune encephalomyelitis. FASEB J. 1993 Apr 1;7(6):592–600. doi: 10.1096/fasebj.7.6.8472896. [DOI] [PubMed] [Google Scholar]
  28. Ritchie M. H., Oakes J. E., Lausch R. N. Passive transfer of anti-herpes simplex virus type 2 monoclonal and polyclonal antibodies protect against herpes simplex virus type 1-induced but not herpes simplex virus type 2-induced stromal keratitis. Invest Ophthalmol Vis Sci. 1993 Jul;34(8):2460–2468. [PubMed] [Google Scholar]
  29. Rollins B. J., Morrison E. D., Stiles C. D. Cloning and expression of JE, a gene inducible by platelet-derived growth factor and whose product has cytokine-like properties. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3738–3742. doi: 10.1073/pnas.85.11.3738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Russell R. G., Nasisse M. P., Larsen H. S., Rouse B. T. Role of T-lymphocytes in the pathogenesis of herpetic stromal keratitis. Invest Ophthalmol Vis Sci. 1984 Aug;25(8):938–944. [PubMed] [Google Scholar]
  31. Schall T. J., Bacon K. B. Chemokines, leukocyte trafficking, and inflammation. Curr Opin Immunol. 1994 Dec;6(6):865–873. doi: 10.1016/0952-7915(94)90006-x. [DOI] [PubMed] [Google Scholar]
  32. Sherry B., Tekamp-Olson P., Gallegos C., Bauer D., Davatelis G., Wolpe S. D., Masiarz F., Coit D., Cerami A. Resolution of the two components of macrophage inflammatory protein 1, and cloning and characterization of one of those components, macrophage inflammatory protein 1 beta. J Exp Med. 1988 Dec 1;168(6):2251–2259. doi: 10.1084/jem.168.6.2251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Springer T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994 Jan 28;76(2):301–314. doi: 10.1016/0092-8674(94)90337-9. [DOI] [PubMed] [Google Scholar]
  34. Staats H. F., Lausch R. N. Cytokine expression in vivo during murine herpetic stromal keratitis. Effect of protective antibody therapy. J Immunol. 1993 Jul 1;151(1):277–283. [PubMed] [Google Scholar]
  35. Tannenbaum C. S., Koerner T. J., Jansen M. M., Hamilton T. A. Characterization of lipopolysaccharide-induced macrophage gene expression. J Immunol. 1988 May 15;140(10):3640–3645. [PubMed] [Google Scholar]
  36. Taub D. D., Oppenheim J. J. Chemokines, inflammation and the immune system. Ther Immunol. 1994 Aug;1(4):229–246. [PubMed] [Google Scholar]
  37. Tekamp-Olson P., Gallegos C., Bauer D., McClain J., Sherry B., Fabre M., van Deventer S., Cerami A. Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. J Exp Med. 1990 Sep 1;172(3):911–919. doi: 10.1084/jem.172.3.911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wang H. M., Sheu M. M., Stulting R. D., Kaplan H. J. Immunohistochemical evaluation of murine HSV-1 keratouveitis. Curr Eye Res. 1989 Jan;8(1):37–46. doi: 10.3109/02713688909013892. [DOI] [PubMed] [Google Scholar]
  39. de Vos A. F., Klaren V. N., Kijlstra A. Expression of multiple cytokines and IL-1RA in the uvea and retina during endotoxin-induced uveitis in the rat. Invest Ophthalmol Vis Sci. 1994 Oct;35(11):3873–3883. [PubMed] [Google Scholar]

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