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Updated: May 30, 2026
Functional Assessment of Intestinal Permeability and Neutrophil Transepithelial Migration in Mice using a Standardized Intestinal Loop Model
Published on: February 11, 2021
Membrane-associated CD93 regulates leukocyte migration and C1q-hemolytic activity during murine peritonitis
Mallary C Greenlee-Wacker1, Carlos Briseño, Manuel Galvan
1Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556, USA.
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.
Insights
Cell-associated CD93 regulates leukocyte recruitment and complement activation during inflammation. Its absence increases susceptibility to peritonitis, while its presence on specific cell types restores normal inflammatory responses.
Area of Science:
- Immunology
- Inflammation Biology
- Complement System
Background:
- CD93 is a cell surface glycoprotein implicated in inflammation.
- Both membrane-associated and soluble forms (sCD93) of CD93 exist.
- The precise molecular function of CD93 in inflammation remains unclear.
Purpose of the Study:
- To investigate the role of CD93 in regulating inflammatory responses.
- To determine whether cell-associated or soluble CD93 is critical for leukocyte recruitment and complement activation.
Main Methods:
- Utilized CD93-deficient (CD93(-/-)) mice and bone marrow chimeric mice.
- Induced peritonitis using thioglycollate injection.
- Assessed leukocyte infiltration, vascular integrity, and complement C1q-hemolytic activity.
- Analyzed cytokine and chemokine levels using Luminex Multiplex and ELISA.
Main Results:
- CD93(-/-) mice exhibited heightened susceptibility to peritonitis with increased leukocyte infiltration and impaired vascular integrity.
- Deficiency in CD93 led to decreased classical complement pathway activity.
- Expression of CD93 on either hematopoietic or nonhematopoietic cells restored normal leukocyte recruitment and complement activity.
- Elevated sCD93 levels in inflammatory fluid were only observed when CD93 was expressed on nonhematopoietic cells.
Conclusions:
- Cell-associated CD93, rather than soluble CD93, is the primary regulator of leukocyte recruitment and complement activation in murine peritonitis.
- CD93 plays a crucial role in maintaining vascular integrity during inflammatory processes.
