TY - JOUR
T1 - The lectin-like domain of complement receptor 3 protects endothelial barrier function from activated neutrophils
AU - Tsikitis, Vassiliki L.
AU - Morin, Nicole A.
AU - Harrington, Elizabeth O.
AU - Albina, Jorge E.
AU - Reichner, Jonathan S.
PY - 2004/7/15
Y1 - 2004/7/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.173.2.1284
DO - 10.4049/jimmunol.173.2.1284
M3 - Article
C2 - 15240721
AN - SCOPUS:3142690479
SN - 0022-1767
VL - 173
SP - 1284
EP - 1291
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -