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Severe inflammatory defect and reduced viability in CD18 and E-selectin double-mutant mice
S B Forlow1, E J White, S C Barlow
1Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
The Journal of Clinical Investigation
|December 20, 2000
Summary
Dual deficiency in CD18 integrins and E-selectin severely impairs neutrophil recruitment and viability. These adhesion molecules are crucial for inflammatory responses, with no alternative pathways compensating for their loss.
Area of Science:
- Immunology
- Cell Biology
- Hematology
Background:
- CD18-deficient mice exhibit variable leukocyte recruitment defects.
- E-selectin-deficient mice show mild or no neutrophil infiltration defects.
- Combined CD18 and E-selectin deficiency leads to significantly reduced viability.
Purpose of the Study:
- To investigate the mechanisms behind the reduced viability in CD18(-/-)CD62E(-/-) mice.
- To explore the cooperative role of E-selectin and CD18 integrins in neutrophil recruitment.
- To determine if alternative adhesion pathways can compensate for the loss of these molecules.
Main Methods:
- Generating CD18(-/-)CD62E(-/-) mice via crossbreeding and bone marrow reconstitution.
- Utilizing a TNF-alpha-induced inflammation model to assess leukocyte recruitment.
- Analyzing leukocyte rolling velocity, adhesion efficiency, hematopoiesis, and cytokine levels.
Main Results:
- CD18(-/-)CD62E(-/-) mice exhibited tenfold-increased leukocyte rolling velocities.
- Leukocyte adhesion efficiency was reduced by 95% in these mice.
- Severe alterations in hematopoiesis, including neutrophilia and elevated G-CSF/GM-CSF, were observed.
Conclusions:
- Cooperation between E-selectin and CD18 integrins is essential for effective neutrophil recruitment.
- The inability to mount an adequate inflammatory response contributes to the reduced viability.
- Alternative adhesion pathways cannot compensate for the combined absence of E-selectin and CD18 integrins.