title: Membrane-associated CD93 regulates leukocyte migration and C1q-hemolytic activity during murine peritonitis.
abstract: CD93 is emerging as a novel regulator of inflammation; however, its molecular function is unknown. CD93 exists as a membrane-associated glycoprotein on the surface of cells involved in the inflammatory cascade, including endothelial and myeloid cells. A soluble form (sCD93) is detectable in blood and is elevated with inflammation. In this study, we demonstrate heightened susceptibility to thioglycollate-induced peritonitis in CD93(-/-) mice. CD93(-/-) mice showed a 1.6-1.8-fold increase in leukocyte infiltration during thioglycollate-induced peritonitis between 3 and 24 h that returned to wild type levels by 96 h. Impaired vascular integrity in CD93(-/-) mice during peritonitis was demonstrated using fluorescence multiphoton intravital microscopy; however, no differences in cytokine or chemokine levels were detected with Luminex Multiplex or ELISA analysis. C1q-hemolytic activity in CD93(-/-) mice was decreased by 22% at time zero and by 46% 3 h after thioglycollate injection, suggesting a defect in the classical complement pathway. Leukocyte recruitment and C1q-hemolytic activity was restored to wild type levels when CD93 was expressed on either hematopoietic cells or nonhematopoietic cells in bone marrow chimeric mice. However, elevated levels of sCD93 in inflammatory fluid were observed only when CD93 was expressed on nonhematopoietic cells. Because cell-associated CD93 was sufficient to restore a normal inflammatory response, these data suggest that cell-associated CD93, and not sCD93, regulates leukocyte recruitment and complement activation during murine peritonitis.
authors.affiliation: Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Mallary C
authors.initials: MC
authors.lastname: Greenlee-Wacker
authors.forename: Carlos
authors.initials: C
authors.lastname: Briseño
authors.forename: Manuel
authors.initials: M
authors.lastname: Galvan
authors.forename: Gabriela
authors.initials: G
authors.lastname: Moriel
authors.forename: Peter
authors.initials: P
authors.lastname: Velázquez
authors.forename: Suzanne S
authors.initials: SS
authors.lastname: Bohlson
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006461:Hemolysis / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010538:Peritonitis / Q000276:immunology / Q000378:metabolism*; D011951:Receptors, Complement / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
chemical_list: D008562:Membrane Glycoproteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D015922:Complement C1q