An association between MMP-9 and impaired T cell migration in ethanol-fed BALB/c mice infected with respiratory syncytial virus-2A

Kristi J. Warren, Jill A. Poole, Jenea M. Sweeter, Jane M. DeVasure, Todd A. Wyatt

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Matrix metalloproteinases are important for proper airway matrix structure and wound healing. These enzymes are also implicated in many airway diseases. Previously, chronic ethanol consumption was shown to prolong inflammation and delay viral clearance in respiratory syncytial virus (RSV)-infected mice. We hypothesize that alcohol alters anti-viral immunity by disrupting immune cell chemotaxis in the lung. BALB/c mice were randomly selected to consume 18% alcohol ad libitum for 8 weeks prior to infection with RSV-2A. Bronchoalveolar lavage (BAL) cell populations were measured by flow cytometry, and chemokines were detected by Western blot or ELISA. MMP-9 levels were determined by polymerase chain reaction (PCR) in mouse lungs and in BAL fluid by ELISA. T cells were acquired from the spleens of water-fed, non-infected control mice (CTRL); alcohol-fed, non-infected (ETOH); water-fed, RSV-infected (RSV); or ethanol-fed, RSV-infected (ETOH-RSV) 4 days after RSV infection. T cells were placed in a transmigration system where chemokines had been treated with and without activated MMP-9. Lymphocyte recruitment was significantly reduced in the BAL 4 days after RSV infection in ETOH-RSV mice, whereas chemokine levels were the highest in this group at all experimental time points examined in comparison to RSV (p < 0.05). MMP-9 mRNA and protein were detected at high levels in ETOH-RSV mice compared to RSV. Using ex vivo transmigration to CCL2 and CXCL10, T cell migration was not impaired between any of the treatment groups, yet when CCL2 and CXCL10 were treated with activated MMP-9, significantly fewer T cells migrated across collagen-coated 5-μm membranes (p < 0.05). Immune cell recruitment is necessary for viral clearance. We show that immune cells are decreased in the lungs of ETOH-RSV mice. In contrast to decreased cell recruitment, key inflammatory chemokines were elevated in the lungs of ETOH-RSV mice. These proteins may be prematurely degraded by MMP-9 in the lung, leading to defective immunity and reduced viral clearance.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalAlcohol
Volume80
DOIs
StatePublished - Nov 2019

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Respiratory Syncytial Viruses
T-cells
Matrix Metalloproteinases
Viruses
Cell Movement
Ethanol
alcohol
immunity
migration
T-Lymphocytes
water
Chemokines
Respiratory Syncytial Virus Infections
Lung
Group
Disease
Alcohols
Bronchoalveolar Lavage
Immunity
Enzyme-Linked Immunosorbent Assay

Keywords

  • Alcohol
  • C-X-C motif chemokine 10
  • Chemokine (C–C motif) ligand 2
  • Ethanol
  • Gelatinase B
  • IL-10
  • Lymphocytes derived from thymus
  • MCP-1
  • Matrix metalloproteinase 9
  • RSV
  • Respiratory syncytial virus
  • T cell

ASJC Scopus subject areas

  • Health(social science)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience

Cite this

An association between MMP-9 and impaired T cell migration in ethanol-fed BALB/c mice infected with respiratory syncytial virus-2A. / Warren, Kristi J.; Poole, Jill A.; Sweeter, Jenea M.; DeVasure, Jane M.; Wyatt, Todd A.

In: Alcohol, Vol. 80, 11.2019, p. 25-32.

Research output: Contribution to journalArticle

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abstract = "Matrix metalloproteinases are important for proper airway matrix structure and wound healing. These enzymes are also implicated in many airway diseases. Previously, chronic ethanol consumption was shown to prolong inflammation and delay viral clearance in respiratory syncytial virus (RSV)-infected mice. We hypothesize that alcohol alters anti-viral immunity by disrupting immune cell chemotaxis in the lung. BALB/c mice were randomly selected to consume 18{\%} alcohol ad libitum for 8 weeks prior to infection with RSV-2A. Bronchoalveolar lavage (BAL) cell populations were measured by flow cytometry, and chemokines were detected by Western blot or ELISA. MMP-9 levels were determined by polymerase chain reaction (PCR) in mouse lungs and in BAL fluid by ELISA. T cells were acquired from the spleens of water-fed, non-infected control mice (CTRL); alcohol-fed, non-infected (ETOH); water-fed, RSV-infected (RSV); or ethanol-fed, RSV-infected (ETOH-RSV) 4 days after RSV infection. T cells were placed in a transmigration system where chemokines had been treated with and without activated MMP-9. Lymphocyte recruitment was significantly reduced in the BAL 4 days after RSV infection in ETOH-RSV mice, whereas chemokine levels were the highest in this group at all experimental time points examined in comparison to RSV (p < 0.05). MMP-9 mRNA and protein were detected at high levels in ETOH-RSV mice compared to RSV. Using ex vivo transmigration to CCL2 and CXCL10, T cell migration was not impaired between any of the treatment groups, yet when CCL2 and CXCL10 were treated with activated MMP-9, significantly fewer T cells migrated across collagen-coated 5-μm membranes (p < 0.05). Immune cell recruitment is necessary for viral clearance. We show that immune cells are decreased in the lungs of ETOH-RSV mice. In contrast to decreased cell recruitment, key inflammatory chemokines were elevated in the lungs of ETOH-RSV mice. These proteins may be prematurely degraded by MMP-9 in the lung, leading to defective immunity and reduced viral clearance.",
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KW - Respiratory syncytial virus

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