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 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 beta2 integrins.
Frenette
P S
PS
Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mayadas
T N
TN
Rayburn
H
H
Hynes
R O
RO
Wagner
D D
DD
D000483:Alleles; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D001483:Base Sequence; D016207:Cytokines / Q000378:metabolism; D019040:E-Selectin / Q000032:analysis / Q000235:genetics*; D004727:Endothelium / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D006410:Hematopoiesis / Q000235:genetics*; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics*; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D007964:Leukocytosis; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D019007:P-Selectin / Q000032:analysis / Q000235:genetics*; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D012867:Skin / Q000276:immunology / Q000473:pathology; D013163:Splenomegaly / Q000276:immunology / Q000473:pathology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014456:Ulcer / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014699:Venules / Q000276:immunology
D016207:Cytokines; D019040:E-Selectin; D019007:P-Selectin