ABSTRACT
CD18-deficient mice (CD18(-/-) mice) have a severe leukocyte recruitment defect in some organs, and no detectable defect in other models. Mice lacking E-selectin (CD62E(-/-) mice) have either no defect or a mild defect of neutrophil infiltration, depending on the model. CD18(-/-)CD62E(-/-), but not CD18(-/-)CD62P(-/-), mice generated by crossbreeding failed to thrive, reaching a maximum body weight of 10-15 grams. To explore the mechanisms underlying reduced viability, we investigated lethally irradiated CD62E(-/-) mice that were reconstituted with CD18(-/-) bone marrow. These mice, but not single-mutant controls, showed tenfold-increased rolling velocities in a TNF-alpha-induced model of inflammation. Leukocyte adhesion efficiency in CD18(-/-)CD62E(-/-) mice was reduced by 95%, and hematopoiesis was drastically altered, including severe bone marrow and blood neutrophilia and elevated G-CSF and GM-CSF levels. The greatly reduced viability of CD18(-/-)CD62E(-/-) mice appears to result from an inability to mount an adequate inflammatory response. Our data show that cooperation between E-selectin and CD18 integrins is necessary for neutrophil recruitment and that alternative adhesion pathways cannot compensate for the loss of these molecules.
Subject(s)
CD18 Antigens/immunology , E-Selectin/immunology , Gene Deletion , Inflammation/immunology , Inflammation/physiopathology , Leukocyte-Adhesion Deficiency Syndrome/immunology , Leukocyte-Adhesion Deficiency Syndrome/pathology , Animals , Body Weight , Bone Marrow Cells/metabolism , Bone Marrow Transplantation , CD18 Antigens/analysis , CD18 Antigens/genetics , Cell Adhesion , Chemotaxis, Leukocyte , E-Selectin/genetics , Failure to Thrive , Female , Granulocyte Colony-Stimulating Factor/blood , Granulocyte-Macrophage Colony-Stimulating Factor/blood , Hemodynamics , Inflammation/pathology , Leukocyte Count , Leukocyte-Adhesion Deficiency Syndrome/genetics , Leukocyte-Adhesion Deficiency Syndrome/physiopathology , Leukocytes/immunology , Leukocytes/metabolism , Leukocytes/pathology , Male , Mice , Mice, Knockout , Organ Size , Phenotype , Skin/pathologyABSTRACT
During routine physical examination, a five-year-old male rhesus macaque (Macaca mulatta) was observed to have gaps in the right iris. Ophthalmic examination revealed inferior and superior iridodialysis with an anterior cortical cataract. The optic nerve head and fundus were normal. Uninvolved areas of the iris and anterior-chamber angle were normal on the basis of results of gonioscopy. Tonometry revealed normal intraocular pressure. The cause of the iridodialysis in this monkey's eye was not known. The animal had been housed individually since arrival due to requirements of the research protocol. Although the concomitant cataract supports a traumatic cause, there was no history of cranial or other ocular injuries. Trauma from fighting through the cage walls, self-trauma or falling inside the cage while under sedation cannot be ruled out. Multiple hematologic evaluations disclosed no abnormalities. This animal did not manifest behavioral abnormalities or any indication of pain. Therefore, treatment was not initiated. Intraocular pressure continues to be monitored at least semiannually.
