Your browser doesn't support javascript.
loading
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.
Afiliación
  • Warren KJ; University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, United States. Electronic address: nomrahjk@gmail.com.
  • Poole JA; University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, United States.
  • Sweeter JM; University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, United States. Electronic address: jenea.sweeter@unmc.edu.
  • DeVasure JM; University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, United States. Electronic address: jdevasure@unmc.edu.
  • Wyatt TA; University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, United States; Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, United States; University of Nebraska Medical Center, Department of
Alcohol ; 80: 25-32, 2019 11.
Article en En | MEDLINE | ID: mdl-30291948
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.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus Sincitiales Respiratorios / Linfocitos T / Quimiotaxis de Leucocito / Infecciones por Virus Sincitial Respiratorio / Metaloproteinasa 9 de la Matriz / Etanol Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Alcohol Asunto de la revista: TRANSTORNOS RELACIONADOS COM SUBSTANCIAS Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus Sincitiales Respiratorios / Linfocitos T / Quimiotaxis de Leucocito / Infecciones por Virus Sincitial Respiratorio / Metaloproteinasa 9 de la Matriz / Etanol Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Alcohol Asunto de la revista: TRANSTORNOS RELACIONADOS COM SUBSTANCIAS Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos