Allergen-induced changes in bone-marrow progenitor and airway dendritic cells in sensitized rats.
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.
Lambrecht
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BN
Department of Respiratory Diseases, University Hospital Ghent, Belgium. bart.lambrecht@rug.ac.be
Carro-Muino
I
I
Vermaelen
K
K
Pauwels
R A
RA
D000818:Animals; D001249:Asthma / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D003713:Dendritic Cells / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000276:immunology; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000032:analysis; D007700:Kinetics; D008297:Male; D010047:Ovalbumin / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology*; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013234:Stem Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D015854:Up-Regulation
D015842:Serine Proteinase Inhibitors; D007073:Immunoglobulin E; D010047:Ovalbumin