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Accessory cells with immunophenotypic and functional features of monocyte-derived dendritic cells are recruited to
A M Tager1, A D Luster, C P Leary
1Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Abstract:
Pulmonary macrophages (Mphi) increase in tissue and bronchoalveolar lavage (BAL) fluid during inflammation caused by bleomycin (BLM). This study demonstrates that increasing numbers of exudate Mphi in BLM lung injury exhibit dendritic cell (DC) features. After the intratracheal administration of BLM (0.075 U), adherent mononuclear cells from the bronchoalveolar lavage fluid (BAMC) of C57BL/6 mice were characterized for morphology, immunophenotype, and accessory cell activities. At day 7 post-BLM, 48% of CD11b+ BAMC displayed features of DC differentiation, as judged by dendritic morphology, expression of class II MHC, 33D1, Factor XIIIa, CD80, and CD86 antigens, and the ability to support a primary allogeneic lymphocyte response (MLR). After BLM treatment, CD11b+ peripheral blood monocytes also showed increased expression of 33D1, Factor XIIIa, CD86, and the ability to stimulate an MLR. We conclude that inflammatory DC with immunophenotypic features of monocyte-derived DC increase in the peripheral blood and lung after an inflammatory stimulus.
Insights
Inflammatory lung injury from bleomycin (BLM) causes an increase in pulmonary macrophages exhibiting dendritic cell (DC) features. These monocyte-derived DCs appear in the blood and lungs, suggesting a role in inflammatory responses.
Area of Science:
- Immunology
- Cell Biology
- Pulmonary Medicine
Background:
- Pulmonary macrophages increase during bleomycin-induced lung inflammation.
- Exudate macrophages in bleomycin lung injury show dendritic cell (DC) characteristics.
Purpose of the Study:
- To characterize the phenotype and function of inflammatory cells in bleomycin-induced lung injury.
- To investigate the differentiation of macrophages into dendritic cells during lung inflammation.
Main Methods:
- Intratracheal administration of bleomycin (BLM) in C57BL/6 mice.
- Characterization of bronchoalveolar lavage fluid (BAMC) cells for morphology, immunophenotype (MHC class II, 33D1, Factor XIIIa, CD80, CD86), and accessory cell function (MLR).
- Analysis of peripheral blood monocytes post-BLM treatment.
Main Results:
- At day 7 post-BLM, 48% of CD11b+ BAMC exhibited DC features, including dendritic morphology and expression of DC markers.
- These cells demonstrated the ability to stimulate allogeneic lymphocyte responses (MLR).
- CD11b+ peripheral blood monocytes also showed increased expression of DC-associated markers and enhanced MLR stimulatory capacity after BLM treatment.
Conclusions:
- Inflammatory dendritic cells (DCs) with monocyte-derived features increase in the lungs and peripheral blood following an inflammatory stimulus.
- These findings highlight a potential role for monocyte-derived DCs in bleomycin-induced lung injury and inflammation.