| First Author | Pruessmeyer J | Year | 2014 |
| Journal | Blood | Volume | 123 |
| Issue | 26 | Pages | 4077-88 |
| PubMed ID | 24833351 | Mgi Jnum | J:213737 |
| Mgi Id | MGI:5585688 | Doi | 10.1182/blood-2013-09-511543 |
| Citation | Pruessmeyer J, et al. (2014) Leukocytes require ADAM10 but not ADAM17 for their migration and inflammatory recruitment into the alveolar space. Blood 123(26):4077-88 |
| abstractText | Inflammation is a key process in various diseases, characterized by leukocyte recruitment to the inflammatory site. This study investigates the role of a disintegrin and a metalloproteinase (ADAM) 10 and ADAM17 for leukocyte migration in vitro and in a murine model of acute pulmonary inflammation. Inhibition experiments or RNA knockdown indicated that monocytic THP-1 cells and primary human neutrophils require ADAM10 but not ADAM17 for efficient chemokine-induced cell migration. Signaling and adhesion events that are linked to cell migration such as p38 and rho GTPase-family activation, F-actin polymerization, adhesion to fibronectin, and up-regulation of alpha5 integrin were also dependent on ADAM10 but not ADAM17. This was confirmed with leukocytes isolated from mice lacking either ADAM10 or ADAM17 in all hematopoietic cells (vav 1 guanine nucleotide exchange factor [Vav]-Adam10(-/-) or Vav-Adam17(-/-) mice). In lipopolysaccharide-induced acute pulmonary inflammation, alveolar recruitment of neutrophils and monocytes was transiently increased in Vav-Adam17(-/-) but steadily reduced in Vav-Adam10(-/-) mice. This deficit in alveolar leukocyte recruitment was also observed in LysM-Adam10(-/-) mice lacking ADAM10 in myeloid cells and correlated with protection against edema formation. Thus, with regard to leukocyte migration, leukocyte-expressed ADAM10 but not ADAM17 displays proinflammatory activities and may therefore serve as a target to limit inflammatory cell recruitment. |
