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Integrin alphaDbeta2 is dynamically expressed by inflamed macrophages and alters the natural history of lethal systemic infections.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2008 Jan 01; Vol. 180 (1), pp. 590-600. - Publication Year :
- 2008
-
Abstract
- The leukocyte integrins have critical roles in host defense and inflammatory tissue injury. We found that integrin alphaDbeta2, a novel but largely uncharacterized member of this family, is restricted to subsets of macrophages and a small population of circulating leukocytes in wild-type mice in the absence of inflammatory challenge and is expressed in regulated fashion during cytokine-induced macrophage differentiation in vitro. alphaDbeta2 is highly displayed on splenic red pulp macrophages and mediates their adhesion to local targets, identifying key functional activity. In response to challenge with Plasmodium berghei, a malarial pathogen that models systemic infection and inflammatory injury, new populations of alphaD+ macrophages evolved in the spleen and liver. Unexpectedly, targeted deletion of alphaD conferred a survival advantage in P. berghei infection over a 30-day observation period. Mechanistic studies demonstrated that the increased survival of alphaD-/- animals at these time points is not attributed to differences in magnitude of anemia or parasitemia or to alterations in splenic microanatomy, each of which is a key variable in the natural history of P. berghei infection, and indicated that an altered pattern of inflammatory cytokines may contribute to the difference in mortality. In contrast to the outcome in malarial challenge, death of alphaD-/- animals was accelerated in a model of Salmonella sepsis, demonstrating differential rather than stereotyped roles for alphaDbeta2 in systemic infection. These studies identify previously unrecognized and unique activities of alphaDbeta2, and macrophages that express it, in host defense and injury.
- Subjects :
- Animals
CD11 Antigens genetics
Cytokines metabolism
Inflammation immunology
Integrin alpha Chains genetics
Liver immunology
Macrophage Activation
Malaria mortality
Mice
Mice, Knockout
Sepsis mortality
Spleen immunology
CD11 Antigens metabolism
Integrin alpha Chains metabolism
Macrophages immunology
Malaria immunology
Plasmodium berghei
Salmonella
Sepsis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 180
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 18097061
- Full Text :
- https://doi.org/10.4049/jimmunol.180.1.590