ICAM-2 mediates neutrophil transmigration in vivo: evidence for stimulus specificity and a role in PECAM-1-independent transmigration.
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.
Cardiovascular Medicine Unit, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
Miao-Tzu
MT
Huang
Karen Y
KY
Larbi
Christoph
C
Scheiermann
Abigail
A
Woodfin
Nicole
N
Gerwin
Dorian O
DO
Haskard
Sussan
S
Nourshargh
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018715:Microscopy, Video; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D010538:Peritonitis / Q000139:chemically induced / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014699:Venules / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C480027:ICAM-2 protein, mouse; D007375:Interleukin-1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha