Allergen-Induced Changes in Bone-Marrow Progenitor and Airway Dendritic Cells in Sensitized Rats

Abstract

Eosinophilic airway inflammation is orchestrated by T-helper (Th)-2 lymphocytes. We have previously demonstrated that dendritic cells (DC) are essential for the presentation of antigen to these Th2 cells leading to airway inflammation. Here, we have examined the presence of DC in the lungs, the kinetics of appearance, and the possible involvement of the bone-marrow progenitor for DC in a rat model of ovalbumin (OVA)-induced airway inflammation. Sensitized rats were exposed to 0, 1, 3, or 7 consecutive daily OVA aerosols. Control rats were sham sensitized and/or exposed to phosphate-buffered saline (PBS), and bronchoalveolar lavage (BAL) was performed 24 h after the last challenge. DC were identified in BAL fluid as low-density, low-autofluorescence, CD3(-), CD45RA-, OX62(+), OX6(+) cells that had long surface extensions and strong costimulatory activity. Low but detectable amounts of BAL DC were seen in sensitized, unexposed animals. After three OVA exposures, the inflammatory infiltrate consisted of CD4(+)-activated T cells, eosinophils, and monocytes. The number of BAL DC was significantly increased in OVA-sensitized/OVA-exposed animals compared with sham-sensitized or PBS-exposed animals. The kinetics of DC increase closely parallelled those in other inflammatory cells. Bone-marrow cells taken from the OVA-sensitized and -exposed group were grown in the DC growth factor granulocyte macrophage colony-stimulating factor for 6 d and the yield of OX62(+)OX6(+) DC was 60% higher compared with PBS-exposed or sham-sensitized animals. We conclude that allergen exposition in sensitized rats increases the number of DC in the airways and the production of progenitors for DC in the bone marrow.

Household Conditions, Eczema Symptoms and Rhinitis Symptoms: Relationship with Wheeze and Severe Wheeze in Children Living in the Polokwane Area, South Africa

“…Inhalation of allergens results in presentation by local dendritic cells to T cells in environment rich in T H 2 cytokines, promoting an allergic response in the airways [67]. These interactions lead to activation of eosinophils, induction of IgE production, mast cell proliferation, epithelial cell activation, mucus hypersecretion, and smooth muscle proliferation observed in asthma [68].…”

The Accumulation of Dendritic Cells in the Lung Is Impaired in CD18−/− But Not in ICAM-1−/− Mutant Mice

“…Previous studies suggested that precursor DCs enter the lung where they differentiate into MHC class II ϩ DC (18,19). At present, little is known about the mechanisms that enable DC precursors to migrate from the blood to the lung, either during steadystate turnover (11) or in response to chemotactic gradients initiated by inhaled Ags (32).…”

A Single Intratracheal Dose of the Growth Factor Fms-Like Tyrosine Kinase Receptor-3 Ligand Induces a Rapid Differential Increase of Dendritic Cells and Lymphocyte Subsets in Lung Tissue and Bronchoalveolar Lavage, Resulting in an Increased Local Antibody Production

“…Isotypematched Abs served as a control. DC were identified as low-autofluorescence cells, non-T and non-B lymphocytes, and double positive for Ox6 (MHC class II) and Ox62 (DC marker) (24). For characterization of the MHC class II/Ox62 ϩ DC, cells were stained with Abs against CD80, CD86, CD11c, and CD54, and the mean fluorescence intensity (MFI) was measured.…”