Adhesion molecule mechanisms mediating monocyte migration through synovial fibroblast and endothelium barriers: role for CD11/CD18, very late antigen-4 (CD49d …

X Shang, BJ Lang, AC Issekutz - The Journal of Immunology, 1998 - journals.aai.org
X Shang, BJ Lang, AC Issekutz
The Journal of Immunology, 1998journals.aai.org
Monocytes migrate through vascular endothelium, and then in connective tissue. As a model
of this process, we investigated adhesion molecules involved in monocyte migration through
HUVEC and a barrier of human synovial fibroblasts (HSF). Minimal spontaneous monocyte
migration (6–7%) occurred through either cell barrier, but this increased markedly (27–35%
of added monocytes) when a C5a chemotactic gradient was present. Migration across
unstimulated HUVEC was partially inhibited (40%) by mAb to CD18 (β 2 integrin) and …
Abstract
Monocytes migrate through vascular endothelium, and then in connective tissue. As a model of this process, we investigated adhesion molecules involved in monocyte migration through HUVEC and a barrier of human synovial fibroblasts (HSF). Minimal spontaneous monocyte migration (6–7%) occurred through either cell barrier, but this increased markedly (27–35% of added monocytes) when a C5a chemotactic gradient was present. Migration across unstimulated HUVEC was partially inhibited (40%) by mAb to CD18 (β 2 integrin) and completely blocked by anti-CD18 plus anti-α 4 (CD49d; very late Ag-4 (VLA-4)) mAbs. In contrast, migration across HSF induced by C5a or monocyte chemoattractant protein-1 was not inhibited by mAb to CD18 and was only partially inhibited (33%) in combination with anti-α 4 mAb. The CD18-and VLA-4-independent migration across HSF was completely inhibited by mAb to α 5 of VLA-5. The inhibitory effect of mAbs to VLA-4 and VLA-5 was on the monocyte and required blockade of CD11/CD18 to be observed. In contrast to HSF, no role for VLA-5 in monocyte transendothelial migration was detected. Both HSF and IL-1-stimulated HUVEC expressed vascular cell adhesion molecule-1 (VCAM-1). However, VLA-4-mediated monocyte migration across HSF was only partially dependent on VCAM-1, in contrast to transendothelial migration, which was completely blocked by anti-VCAM-1 mAbs. In conclusion, unlike transendothelial migration, for which VLA-4 is the alternative mechanism to CD11/CD18 on monocytes, both VLA-4 and VLA-5 can mediate monocyte migration through fibroblast barriers. In addition to VCAM-1, other ligand (s) on HSF are also involved in the VLA-4-mediated migration.
journals.aai.org