Susceptibility to Infection and Altered Hematopoiesis in Mice Deficient in Both P- and E-Selectins

We describe the phenotype of mice lacking both endothelial selectins after sequential ablation of the genes encoding P- and E-selectins. In contrast with the rather mild phenotypes observed in mice deficient in a single selectin gene, the doubly deficient mice present extreme leukocytosis, elevated...

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Bibliographic Details
Published in:Cell 1996-02, Vol.84 (4), p.563-574
Main Authors: Frenette, Paul S, Mayadas, Tanya N, Rayburn, Helen, Hynes, Richard O, Wagner, Denisa D
Format: Article
Language:English
Subjects:
Alleles
Animals
Bacterial Infections - immunology
Base Sequence
Cytokines - metabolism
E-Selectin - analysis
E-Selectin - genetics
Endothelium - chemistry
Endothelium - cytology
Endothelium - immunology
Hematopoiesis - genetics
Leukocyte-Adhesion Deficiency Syndrome - genetics
Leukocytes - cytology
Leukocytes - immunology
Leukocytosis
Mice
Mice, Inbred Strains
Mice, Transgenic
Molecular Sequence Data
Neutrophils - cytology
Neutrophils - immunology
P-Selectin - analysis
P-Selectin - genetics
Peritonitis - chemically induced
Peritonitis - immunology
Peritonitis - pathology
Phenotype
Skin - immunology
Skin - pathology
Splenomegaly - immunology
Splenomegaly - pathology
Stem Cells - cytology
Stem Cells - physiology
Ulcer - immunology
Ulcer - microbiology
Ulcer - pathology
Venules - immunology
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Summary:We describe the phenotype of mice lacking both endothelial selectins after sequential ablation of the genes encoding P- and E-selectins. In contrast with the rather mild phenotypes observed in mice deficient in a single selectin gene, the doubly deficient mice present extreme leukocytosis, elevated cytokine levels, and alterations in hematopoiesis. Granulocytopoiesis is increased both in bone marrow and spleen, while erythropoiesis is partially translocated to the spleen. Virtual lack of leukocyte rolling and low extravasation at sites of inflammation make these animals susceptible to opportunistic bacterial infections, to which they succumb. Our results show that the absence of endothelial selectins severely affects leukocyte homeostasis and indicate that these two selectins are as important for normal leukocyte function as are the leukocyte β2 integrins.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)81032-6