The lectin-like domain of complement receptor 3 protects endothelial barrier function from activated neutrophils

Vassiliki L. Tsikitis, Nicole A. Morin, Elizabeth O. Harrington, Jorge E. Albina, Jonathan S. Reichner

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


The adhesion of neutrophils to endothelial cells is a central event leading to diapedesis and involves the binding of the I-domain of β2 integrins (CD11/CD18) to endothelial ICAMs. In addition to the I-domain, the β2 integrin complement receptor 3 (CR3) (CD11b/CD18) contains a lectin-like domain (LLD) that can alter leukocyte functions such as chemotaxis and cytotoxicity. The present study demonstrates that, in contrast to the CR3 I-domain, Ab blockade of the CR3 LLD has no role in mediating neutrophil-induced loss of endothelial barrier function. However, activation of CR3 with the LLD agonist β-glucan protects the barrier function of endothelial cells in the presence of activated neutrophils and reduces transendothelial migration without affecting adhesion of the neutrophils to the endothelium. The LLD site-specific mAb VIM12 obviates β-glucan protection while activation of the LLD by VLM12 cross-linking mimics the β-glucan response by both preserving endothelial barrier function and reducing neutrophil transendothelial migration. β-glucan has no direct effect on endothelial cell function in the absence of activated neutrophils. These findings demonstrate that signaling through the CR3 LLD prevents neutrophil-induced loss of endothelial barrier function and reduces diapedesis. This suggests that the LLD may be a suitable target for oligosaccharide-based antiinflammatory therapeutics.

Original languageEnglish (US)
Pages (from-to)1284-1291
Number of pages8
JournalJournal of Immunology
Issue number2
StatePublished - Jul 15 2004
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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