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ICAM-2 mediates neutrophil transmigration in vivo: evidence for stimulus specificity and a role in PECAM-1-independent transmigration

Huang, Miao-Tzu
Larbi, Karen Y
Woodfin, Abigail
Gerwin, Nicole
Haskard, Dorian O
Nourshargh, Sussan
Published in Blood. 2006, vol. 107, no. 12, p. 4721-4727
Abstract ICAM-2 has been implicated in leukocyte transmigration in vitro, but there is little in vivo evidence to support this. To address this, neutrophil migration was investigated in ICAM-2-deficient mice (KO) and in wild-type (WT) mice treated with an anti-ICAM-2 blocking monoclonal antibody (mAb) (3C4). In a peritonitis model, IL-1beta-induced accumulation of neutrophils was significantly reduced in mice treated with 3C4 (51% inhibition) and in KO mice (41% inhibition). In contrast, TNF-alpha- or thioglycolate-induced responses were not suppressed in KO mice. Analysis of IL-1beta-induced leukocyte responses in cremasteric venules of KO animals by intravital microscopy indicated a defect in transmigration (44% inhibition) but not rolling or adhesion. As found before, TNF-alpha-induced leukocyte transmigration was unaltered in the KO mice. WT mice treated with the anti-ICAM-2 mAb also exhibited a selective reduction in leukocyte transmigration in response to IL-1beta while an anti-ICAM-1 mAb inhibited both leukocyte adhesion and transmigration. Interestingly, mAb 3C4 significantly suppressed IL-1beta-induced neutrophil transmigration in PE-CAM-1 KO animals in the peritonitis model but not in the cremaster muscle. The findings provide direct evidence for the involvement of ICAM-2 in neutrophil transmigration in vivo, though this role appears to be stimulus specific. Furthermore, ICAM-2 appears capable of mediating PECAM-1-independent leukocyte transmigration.
Keywords AnimalsAntibodies, Monoclonal/administration & dosage/immunologyAntigens, CD/immunology/metabolismCell Adhesion/drug effects/physiologyCell Adhesion Molecules/deficiency/immunology/metabolismCell Movement/drug effects/physiologyDisease Models, AnimalFemaleInterleukin-1/metabolismMiceMice, KnockoutMicroscopy, VideoNeutrophils/cytology/metabolismPeritonitis/chemically induced/metabolismPlatelet Endothelial Cell Adhesion Molecule-1/genetics/metabolismTumor Necrosis Factor-alpha/metabolismVenules/metabolism
PMID: 16469869
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Research group L'influence du rôle du cycle circadien sur l'immunité (995)
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HUANG, Miao-Tzu et al. ICAM-2 mediates neutrophil transmigration in vivo: evidence for stimulus specificity and a role in PECAM-1-independent transmigration. In: Blood, 2006, vol. 107, n° 12, p. 4721-4727. doi: 10.1182/blood-2005-11-4683

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Deposited on : 2019-01-31

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