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Journal of Virology, January 2001, p. 878-890, Vol. 75, No. 2
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.2.878-890.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Inducible Expression of Inflammatory Chemokines in Respiratory
Syncytial Virus-Infected Mice: Role of MIP-1
in Lung
Pathology
Helene A.
Haeberle,1,2
William A.
Kuziel,3
Hans-Juergen
Dieterich,2
Antonella
Casola,1
Zoran
Gatalica,4 and
Roberto
P.
Garofalo1,5,*
Departments of
Pediatrics,1
Pathology,4 and Microbiology and
Immunology,5 The University of Texas Medical
Branch, Galveston, and Department of Genetics and Microbiology,
University of Texas, Austin,3 Texas,
and Department of Anesthesiology, Universitaetsklinikum,
Tuebingen, Germany2
Received 15 May 2000/Accepted 13 October 2000
Lower respiratory tract disease caused by respiratory syncytial
virus (RSV) is characterized by profound airway mucosa inflammation, both in infants with naturally acquired infection and in experimentally inoculated animal models. Chemokines are central regulatory molecules in inflammatory, immune, and infectious processes of the lung. In this
study, we demonstrate that intranasal infection of BALB/c mice with RSV
A results in inducible expression of lung chemokines belonging to the
CXC (MIP-2 and IP-10), CC (RANTES, eotaxin, MIP-1
, MIP-1
,
MCP-1, TCA-3) and C (lymphotactin) families. Chemokine mRNA expression
occurred as early as 24 h following inoculation and persisted for
at least 5 days in mice inoculated with the highest dose of virus
(107 PFU). In general, levels of chemokine mRNA and protein
were dependent on the dose of RSV inoculum and paralleled the intensity
of lung cellular inflammation. Immunohisthochemical studies indicated that RSV-induced expression of MIP-1
, one of the most abundantly expressed chemokines, was primarily localized in epithelial cells of
the alveoli and bronchioles, as well as in adjoining capillary endothelium. Genetically altered mice with a selective deletion of the
MIP-1
gene (
/
mice) demonstrated a significant reduction in lung
inflammation following RSV infection, compared to control littermates
(+/+ mice). Despite the paucity of infiltrating cells, the peak RSV
titer in the lung of
/
mice was not significantly different from
that observed in +/+ mice. These results provide the first direct
evidence that RSV infection may induce lung inflammation via the early
production of inflammatory chemokines.
*
Corresponding author. Mailing address: Division of
Immunology/Allergy/Rheumatology, 301 University Blvd., Galveston, TX
77555-0369. Phone: (409) 772-2658. Fax: (409) 772-1761. E-mail:
rpgarofa{at}utmb.edu.
Journal of Virology, January 2001, p. 878-890, Vol. 75, No. 2
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.2.878-890.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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