Abstract
Leukocyte recruitment to sites of inflammation requires the functions of selectins and integrins. P-selectin null (CD62P-/-) mice show a mild and CD18 null (CD18-/-) mice a more severe neutrophil recruitment defect in some inflammatory models. To investigate the possible cooperative interactions between CD18 integrins and P-selectin in mediating neutrophil recruitment, we generated CD18-/-CD62P-/- double null mice. CD18-/-CD62P-/- mice were apparently normal at weaning and fertile but later failed to gain weight, showed increased susceptibility to infection by fecal and commensal bacteria, and survived only 5-6 months. Some CD18-/-CD62P-/- mice showed severe spontaneous skin lesions; most showed neutrophil infiltration in the lungs and liver, and positive bacterial cultures from internal organs. The number and velocity of rolling leukocytes in tumor necrosis factor α treated venules of CD18-/-CD62P-/- mice was similar to those in wild-type mice, but neutrophil adhesion was severely reduced. Only 25% of adhered leukocytes were neutrophils in CD18-/-CD62P-/-mice vs. >90% in wild-type, CD62P-/-, and CD 18-/- single mutants. Our data show that removing both P-selectin and CD18 integrins from mice leads to severe neutrophil recruitment defects and spontaneous pathology.
Original language | English (US) |
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Pages (from-to) | 1488-1496 |
Number of pages | 9 |
Journal | FASEB Journal |
Volume | 16 |
Issue number | 12 |
DOIs | |
State | Published - Oct 2002 |
Externally published | Yes |
Keywords
- Adhesion molecules
- Inflammation
- Integrins
- Intravital microscopy
- Knockout
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics