α1β1 Integrin-Mediated Adhesion Inhibits Macrophage Exit from a Peripheral Inflammatory Lesion

Abstract

Integrins are adhesion molecules critical for the recruitment of leukocytes from blood into peripheral tissues. However, whether integrins are also involved in leukocyte exit from peripheral tissues via afferent lymphatics to the draining lymph node remains poorly understood. In this article, we show that adhesion by the collagen IV–binding integrin α1β1 unexpectedly inhibited macrophage exit from inflamed skin. We monitored macrophages exiting mouse footpads using a newly developed in situ pulse labeling technique. Blockade of α1β1 integrin or genetic deletion (Itga1−/−) increased macrophage exit efficiency. Chemotaxis assays through collagen IV showed more efficient migration of Itga1−/− macrophages relative to wild type. Given that macrophages are key orchestrators of inflammation, α1β1 integrin adhesion may represent a mechanism for regulating inflammatory responses by controlling macrophage exit or persistence in inflamed tissues.

Toxoplasma gondii‐infected natural killer cells display a hypermotility phenotype in vivo

“…Intermediate levels of integrinmediated adhesion are usually optimal for cell migration, whereas too much or too little adhesion can negatively impact cell motility. 33 Thus, the reduction in cell spreading and LFA-1 clustering observed in T. gondii-infected NK cells is consistent with the changes in motility observed in vivo, and implies that NK cells are constantly using LFA-1 to contact other cells or structures in tissues. Similarly, LFA-1 has been implicated in the intranodal migration of T cells, whereas in vitro studies have shown that LFA-1 triggers asymmetrical NK cell spreading and migration.…”

“…Our data reveal that impaired cell spreading and CD11a/LFA‐1 clustering in T. gondii ‐infected NK cells is a possible mechanism for their altered motility in tissues. Intermediate levels of integrin‐mediated adhesion are usually optimal for cell migration, whereas too much or too little adhesion can negatively impact cell motility 33 . Thus, the reduction in cell spreading and LFA‐1 clustering observed in T. gondii ‐infected NK cells is consistent with the changes in motility observed in vivo , and implies that NK cells are constantly using LFA‐1 to contact other cells or structures in tissues.…”

APE1/Ref‐1 knockdown in pancreatic ductal adenocarcinoma – characterizing gene expression changes and identifying novel pathways using single‐cellRNAsequencing

“…ITGA1, part of the integrin signaling and virus entry via endocytic pathways as identified by IPA, is involved in cell proliferation (Macias‐Perez et al ., 2008) and invasion (Yang et al ., 2015), as well as inflammation (Becker et al ., 2013) and fibrosis (Ramos et al ., 2012), which have all been previously linked to APE1 (Aamann et al ., 2016; Shah et al ., 2017). …”

Integrin signaling in atherosclerosis

“…To facilitate cell migration, macrophages express several extracellular matrix-binding integrins, including the collagen receptor α1β1, the laminin receptors α3β1 and α6β1, and the provisional matrix-binding integrins α4β1, α5β1, α9β1, αvβ3, and αvβ5 [139–143]. Ligation of α1β1 on collagen limits macrophage egression from inflamed tissue [139], and α1-deficient mice show reduced plaque macrophage and T cell content [144]. Osteopontin, known to be expressed in atherosclerotic plaques, interacts with the monocyte integrins α4β1, α9β1, and αvβ3, and promotes monocyte migration and survival [145].…”