Lymphocyte Trafficking and Regional Immunity

Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

“…One of the most striking features is the unusual co-expression of MAdCAM-1 and P-selectin on vessels of the vascular zone. MAdCAM-1, which directs lymphocyte traffic through venules in mucosal tissues in adult mice, mediates adhesion of leukocytes via the a4b7-integrin homing receptor [12,13]. Interestingly, the MAdCAM-1 + P-selectin + vessels as well as the surrounding tissue of the vascular zone contain large numbers of cells of the monocyte/macrophage lineage.…”

“…Similar results were seen in implantation sites of syngeneic pregnancies of mice lacking P-selectin as well as of P-selectin -/-mice treated with MECA-367 in comparison to untreated or Hermes-1-treated syngeneic pregnancies on the same genetic background. Current models suggest that the specificity of leukocyte trafficking is based on the sequential involvement of combinations of selectin, a4-integrin and b2-integrin mediating initial contact, rolling and activation-dependent adhesion [12,13]. The unusual co-expression of P-selectin (partially associated with platelets) and MAdCAM-1 at this site may provide a mechanism for selecting specialized subsets of leukocytes displaying a combination of P-selectin-and MAdCAM-1-binding activities (e.g.…”

“…The a4b1-integrin binds to VCAM-1, which is induced on endothelium in nonmucosal sites of inflammation. VCAM-1 can also mediate adhesion through activated a4b7-integrin, but this interaction may require a higher state of integrin activation than that needed for binding to MAdCAM-1 (reviewed in [12,13]). The b2-integrins appear specialized to support secondary activation-dependent adhesion and arrest of trafficking leukocytes.…”

Therapeutic targeting of α4-integrins in chronic inflammatory diseases: tipping the scales of risk towards benefit?

“…a4b1 is also known as very late antigen (VLA)-4 or CD49d/CD29, while a4b7 is sometimes referred to as lamina propria associated molecule (LPAM)-1. a4-integrins are abundantly expressed on lymphocytes, monocytes, and eosinophils but low on neutrophils [16]. The primary ligand for a4b1-integrin on endothelium is vascular cell adhesion molecule (VCAM)-1, while MAdCAM-1 is the principal counter-receptor for a4b7 [16].…”

“…a4b1 is also known as very late antigen (VLA)-4 or CD49d/CD29, while a4b7 is sometimes referred to as lamina propria associated molecule (LPAM)-1. a4-integrins are abundantly expressed on lymphocytes, monocytes, and eosinophils but low on neutrophils [16]. The primary ligand for a4b1-integrin on endothelium is vascular cell adhesion molecule (VCAM)-1, while MAdCAM-1 is the principal counter-receptor for a4b7 [16]. Under physiological conditions, a4b7 mediates the homing of naïve lymphocytes into gut associated lymphoid tissues such as the mesenteric lymph nodes and the Peyer's patches via binding to MAdCAM-1, which is constitutively expressed on high endothelial venules.…”