Pretreatment with Recombinant Human Vascular Endothelial Growth Factor Reduces Virus Replication and Inflammation in a Perinatal Lamb Model of Respiratory Syncytial Virus Infection

David K Meyerholz; Jack M Gallup; Tatjana Lazic; Marcia M.A De Macedo; Howard D Lehmkuhl; Mark R Ackermann

doi:10.1089/vim.2006.0089

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Pretreatment with Recombinant Human Vascular Endothelial Growth Factor Reduces Virus Replication and Inflammation in a Perinatal Lamb Model of Respiratory Syncytial Virus Infection

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Pretreatment with Recombinant Human Vascular Endothelial Growth Factor Reduces Virus Replication and Inflammation in a Perinatal Lamb Model of Respiratory Syncytial Virus Infection

David K Meyerholz, Jack M Gallup, Tatjana Lazic, Marcia M.A De Macedo, Howard D Lehmkuhl and Mark R Ackermann

Viral immunology, Vol.20(1), pp.188-196

2007

DOI: 10.1089/vim.2006.0089

PMCID: PMC2791062

PMID: 17425433

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Abstract

Vascular endothelial growth factor (VEGF) is increasingly recognized as a perinatal regulator of lung maturation and surfactant protein expression. Preterm and young infants are at increased risk for pulmonary immaturity characterized by insufficient surfactant production as well as increased risk for severe manifestations of respiratory syncytial virus (RSV) infection. Innate immune components including surfactant proteins A and D, and β-defensins have putative antimicrobial activity against pulmonary pathogens including RSV. Our hypothesis was that recombinant human VEGF (rhVEGF) pretreatment therapy would decrease RSV disease in the perinatal lamb RSV model. Newborn lambs were pretreated with rhVEGF, betamethasone, or saline and then inoculated with bovine RSV or sterile medium. Tissues were collected 5 d postinoculation, corresponding to the initiation of severe lesions and peak viral replication. In RSV-infected lambs, rhVEGF therapy increased the mean daily body temperature, decreased airway neutrophil exudate, and reduced RSV replication compared with betamethasone or saline pretreatment. Furthermore, rhVEGF therapy significantly mitigated the RSV-induced increase in surfactant protein A mRNA expression and decrease in surfactant protein D mRNA expression. In control (non-RSV-infected) lambs, pretreatment with rhVEGF increased sheep β-defensin-1 (SBD1) mRNA expression, but no alteration in surfactant proteins A and D was detected. This novel study demonstrates that rhVEGF pretreatment mitigates RSV disease and, in addition, rhVEGF regulation of innate immune genes is dependent on RSV infection status.

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Title: Subtitle: Pretreatment with Recombinant Human Vascular Endothelial Growth Factor Reduces Virus Replication and Inflammation in a Perinatal Lamb Model of Respiratory Syncytial Virus Infection
Creators: David K Meyerholz - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa
Jack M Gallup - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa
Tatjana Lazic - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa
Marcia M.A De Macedo - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa
Howard D Lehmkuhl - National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, Iowa
Mark R Ackermann - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa
Resource Type: Journal article
Publication Details: Viral immunology, Vol.20(1), pp.188-196
DOI: 10.1089/vim.2006.0089
PMID: 17425433
PMCID: PMC2791062
NLM abbreviation: Viral Immunol
ISSN: 0882-8245
eISSN: 1557-8976
Language: English
Date published: 2007
Academic Unit: Pathology
Record Identifier: 9984083257502771

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