VLA-4 integrin can mediate CD11/CD18-independent transendothelial migration of human monocytes.

Abstract

The migration of human monocytes across unactivated and activated human umbilical vein endothelium (HUVE) in response to chemotactic factors was studied, and the adhesion molecules involved were characterized. Migration of blood monocytes or U937 cell line-derived monocytes across unactivated HUVE induced by C5a, was partially inhibited (by 75%) by mAbs (R15.7 or 60.3) to CD18 of the CD11/CD18 complex on the monocyte. However, when the HUVE was pretreated for 5 h with IL-la (0.1 ng/ml), TNF-a (100 U/ml), or LPS (1 ng/ml), migration induced by C5a was no longer inhibited; i.e., migration became CD18 independent. The monocyte CD18-independent migration was completely blocked by mAbs against a4 or 01 integrin chains of VLA4. This migration was also partially inhibited by mAbs against vascular cell adhesion molecule-i (VCAM-1), a major counter-receptor on HUVE for VLA4, but not by mAbs to E-selectin or intercellular adhesion molecule-i. The significant CD18-independent migration across "unactivated" HUVE was also inhibited by mAbs against a4 or #I chains of VLA4, although mAbs against VCAM-1 did not inhibit under these conditions. Finally, considerable VLA4-dependent transendothelial migration to C5a was also observed with monocytes from a patient with CD18 deficiency (leukocyte adhesion deficiency). These results suggest that (a) there is a major CD18-independent component in monocyte chemotactic factor-dependent migration across activated and unactivated endothelium; (b) that VLA4 integrin on the monocyte has a major role in this migration; and (c) that VCAM-1 on activated endothelium functions as a counter-receptor in this process, but other ligands for VLA4, especially on unactivated endothelium, may also be involved. (J. Clin. Invest. 1993. 92:2768-2777

Interleukin-1.BETA. Stimulates Transendothelial Mobilization of Human Peripheral Blood Mononuclear Cells with a Potential to Differentiate into Osteoclasts in the Presence of Osteoblasts.

“…The present study revealed that the IL-1/3-stimulated migration is not mediated through its action on either PBMCs or SaOS-2 cells, but through its action on HUVECs. The present results were consistent with previous reports that transendothelial migration of leukocytes including monocytes occurred through the activation of endothelium with IL-1 [18,19]. Once penetrated across endothelium, PBMCs should migrate through extravascular spaces and anchor to stroma and/or stromal cells including osteoblasts.…”

“…In several previous studies, monocytes were cocultured only with endothelial monolayers for their transmigration experiments [18,19]. To reproduce their transmigration in bone tissue, we established a coculture system consisting of three different cells: PBMCs, HUVECs and SaOS-2 cells.…”

“…In contrast, the migration of PBMCs was not stimulated with IL-l jS in either case, suggesting that the transendothelial migration of PBMCs did not occur through the direct action of IL-13 on PBMCs. Several reports [18,19] revealed that transmigration of monocytes across IL-113-activated HUVECs was mainly dependent upon X32-integrin. In the present study, we confirmed it (data not shown).…”

“…Repetitive examination revealed that dense grains due to the binding In bone tissue, monocytes are often found in the extravascular spaces adjacent to bone-resorbing surfaces [21], although their precise origin and roles in bone remodeling remain to be determined. Monocyte infiltration is thought to be triggered by various chemoattractants and cytokines including IL-1 [18,19]. Increased secretion levels of IL-1 activity by PBMCs have been reported in postmenopausal women [13].…”

P-selectin and MAC-1 mediate monocyte rolling and adhesion to ECM-bound platelets under flow conditions

“…Selectin-ligands are glycoproteins bearing sialylated Lewis x , such as P-selectin glycoprotein ligand-1 (PSGL-1), Glycam-1, and the CD34 antigen [6,7]. Firm monocyte adhesion is mediated by integrins, such as LFA-1 (CD11a/CD18), MAC-1 (CD11b/CD18), and VLA-4 (CD49d/CD29) [8][9][10]. PECAM-1 (CD31) is an adhesion molecule of the immunoglobulin-gene superfamily which plays a role in leukocyte extravasation [11,12].…”