Severe inflammatory defect and reduced viability in CD18 and E-selectin double-mutant mice

S. B. Forlow, E. J. White, S. C. Barlow, S. H. Feldman, H. Lu, G. J. Bagby, A. L. Beaudet, D. C. Bullard, K. Ley

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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-α-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.

Original languageEnglish (US)
Pages (from-to)1457-1466
Number of pages10
JournalJournal of Clinical Investigation
Issue number12
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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