Abstract
In this study we have shown, for the first time, that Japanese encephalitis virus (JEV) and a low molecular weight (10 kDa) macrophage-derived neutrophil chemotactic factor (MDF) produced following JEV infection in mice could cause an alteration in the permeability of the blood-brain barrier resulting in leakage of plasma protein bound Evans blue dye and radiolabelled erythrocytes in brain. The maximum leakage occurred at day 6 after intracerebral (i.c.) JEV infection and was sensitive to anti-JEV antisera. Further, MDF caused peak leakage of dye and radiolabelled erythrocytes at 1 h post inoculation with a decline thereafter. Complete restoration of the integrity of the blood-brain barrier occurred by the 4th hour. The extent of leakage was dose dependent and showed a direct correlation between the level of MDF, clinical sickness and virus titre in brain. Anti-MDF antisera protected the mice against the effects of MDF. These findings show that JEV-induced cytokine, MDF, alters the integrity of the blood-brain barrier and thus controls the cellular and plasma leakage into the CNS.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bharadwaj M., Khanna N., Mathur A., Chaturvedi U. C. Effect of macrophage-derived factor on hypoferraemia induced by Japanese encephalitis virus in mice. Clin Exp Immunol. 1991 Feb;83(2):215–218. doi: 10.1111/j.1365-2249.1991.tb05617.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Björk J., Hugli T. E., Smedegård G. Microvascular effects of anaphylatoxins C3a and C5a. J Immunol. 1985 Feb;134(2):1115–1119. [PubMed] [Google Scholar]
- Chaturvedi U. C., Mathur A., Tandon P., Natu S. M., Rajvanshi S., Tandon H. O. Variable effect on peripheral blood leucocytes during JE virus infection of man. Clin Exp Immunol. 1979 Dec;38(3):492–498. [PMC free article] [PubMed] [Google Scholar]
- Chen W. R., Tesh R. B., Rico-Hesse R. Genetic variation of Japanese encephalitis virus in nature. J Gen Virol. 1990 Dec;71(Pt 12):2915–2922. doi: 10.1099/0022-1317-71-12-2915. [DOI] [PubMed] [Google Scholar]
- Colditz I., Zwahlen R., Dewald B., Baggiolini M. In vivo inflammatory activity of neutrophil-activating factor, a novel chemotactic peptide derived from human monocytes. Am J Pathol. 1989 Apr;134(4):755–760. [PMC free article] [PubMed] [Google Scholar]
- Hase T., Dubois D. R., Summers P. L. Comparative study of mouse brains infected with Japanese encephalitis virus by intracerebral or intraperitoneal inoculation. Int J Exp Pathol. 1990 Dec;71(6):857–869. [PMC free article] [PubMed] [Google Scholar]
- Johnson R. T., Burke D. S., Elwell M., Leake C. J., Nisalak A., Hoke C. H., Lorsomrudee W. Japanese encephalitis: immunocytochemical studies of viral antigen and inflammatory cells in fatal cases. Ann Neurol. 1985 Nov;18(5):567–573. doi: 10.1002/ana.410180510. [DOI] [PubMed] [Google Scholar]
- Johnson R. T. Inflammatory response to viral infection. Res Publ Assoc Res Nerv Ment Dis. 1971;49:305–312. [PubMed] [Google Scholar]
- Johnson R. T., Intralawan P., Puapanwatton S. Japanese encephalitis: identification of inflammatory cells in cerebrospinal fluid. Ann Neurol. 1986 Dec;20(6):691–695. doi: 10.1002/ana.410200607. [DOI] [PubMed] [Google Scholar]
- Khanna N., Agnihotri M., Mathur A., Chaturvedi U. C. Neutrophil chemotactic factor produced by Japanese encephalitis virus stimulated macrophages. Clin Exp Immunol. 1991 Nov;86(2):299–303. doi: 10.1111/j.1365-2249.1991.tb05813.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Mathur A., Bharadwaj M., Kulshreshtha R., Rawat S., Jain A., Chaturvedi U. C. Immunopathological study of spleen during Japanese encephalitis virus infection in mice. Br J Exp Pathol. 1988 Jun;69(3):423–432. [PMC free article] [PubMed] [Google Scholar]
- Mathur A., Chaturvedi U. C., Tandon H. O., Agarwal A. K., Mathur G. P., Nag D., Prasad A., Mittal V. P. Japanese encephalitis epidemic in Uttar Pradesh, India during 1978. Indian J Med Res. 1982 Feb;75:161–169. [PubMed] [Google Scholar]
- Mathur A., Kulshreshtha R., Chaturvedi U. C. Evidence for latency of Japanese encephalitis virus in T lymphocytes. J Gen Virol. 1989 Feb;70(Pt 2):461–465. doi: 10.1099/0022-1317-70-2-461. [DOI] [PubMed] [Google Scholar]
- Mohanty S., Ray A. K., Dey P. K. Cerebral oedema and blood-brain and blood-CSF barriers in experimental brain trauma: effect of indomethacin-A prostaglandin synthetase inhibitor. Indian J Physiol Pharmacol. 1980 Apr-Jun;24(2):91–96. [PubMed] [Google Scholar]
- Monath T. P., Cropp C. B., Harrison A. K. Mode of entry of a neurotropic arbovirus into the central nervous system. Reinvestigation of an old controversy. Lab Invest. 1983 Apr;48(4):399–410. [PubMed] [Google Scholar]
- Peveri P., Walz A., Dewald B., Baggiolini M. A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med. 1988 May 1;167(5):1547–1559. doi: 10.1084/jem.167.5.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pohajdak B., Gomez J., Orr F. W., Khalil N., Talgoy M., Greenberg A. H. Chemotaxis of large granular lymphocytes. J Immunol. 1986 Jan;136(1):278–284. [PubMed] [Google Scholar]
- Strieter R. M., Kunkel S. L., Showell H. J., Marks R. M. Monokine-induced gene expression of a human endothelial cell-derived neutrophil chemotactic factor. Biochem Biophys Res Commun. 1988 Nov 15;156(3):1340–1345. doi: 10.1016/s0006-291x(88)80779-4. [DOI] [PubMed] [Google Scholar]
- Thumwood C. M., Hunt N. H., Clark I. A., Cowden W. B. Breakdown of the blood-brain barrier in murine cerebral malaria. Parasitology. 1988 Jun;96(Pt 3):579–589. doi: 10.1017/s0031182000080203. [DOI] [PubMed] [Google Scholar]
- Umenai T., Krzysko R., Bektimirov T. A., Assaad F. A. Japanese encephalitis: current worldwide status. Bull World Health Organ. 1985;63(4):625–631. [PMC free article] [PubMed] [Google Scholar]
- Van Damme J., Van Beeumen J., Conings R., Decock B., Billiau A. Purification of granulocyte chemotactic peptide/interleukin-8 reveals N-terminal sequence heterogeneity similar to that of beta-thromboglobulin. Eur J Biochem. 1989 May 1;181(2):337–344. doi: 10.1111/j.1432-1033.1989.tb14729.x. [DOI] [PubMed] [Google Scholar]
- Wedmore C. V., Williams T. J. Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature. 1981 Feb 19;289(5799):646–650. doi: 10.1038/289646a0. [DOI] [PubMed] [Google Scholar]
- Westaway E. G., Brinton M. A., Gaidamovich SYa, Horzinek M. C., Igarashi A., Käriäinen L., Lvov D. K., Porterfield J. S., Russell P. K., Trent D. W. Flaviviridae. Intervirology. 1985;24(4):183–192. doi: 10.1159/000149642. [DOI] [PubMed] [Google Scholar]
- Yoshimura T., Matsushima K., Oppenheim J. J., Leonard E. J. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin 1 (IL 1). J Immunol. 1987 Aug 1;139(3):788–793. [PubMed] [Google Scholar]