title: Immune cell recruitment to inflammatory loci is impaired in mice deficient in basement membrane protein laminin alpha4.
abstract: For leukocytes to penetrate the vessel wall, they need to interact sequentially with the endothelial lining and the perivascular BM. The matrix protein laminin-411 is a major constituent of the vascular BM. The laminin alpha4 chain is a component of laminin-411 and has structural and signaling functions. Here, we addressed the role of BM laminin alpha4 in leukocyte recruitment to inflammatory loci. We used several recruitment models in Lam4(-/-) and WT mice to determine whether lack of laminin-411 in the perivascular BM influences extravasation of inflammatory cells. Recruitment of all major leukocyte subsets (neutrophils, monocytes, and lymphocytes) was reduced in Lam4(-/-) mice compared with WT. With the use of intravital microscopy, we concluded that this decrease was a result of impaired diapedesis through the vessel wall, as neither leukocyte adhesion to the endothelial lining nor migration in extravascular tissue was hampered in Lam4(-/-) mice. Collectively, our data suggest a reduced ability of immune cells to penetrate the vessel wall in mice deficient in laminin alpha4.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden. ellinor.kenne@ki.se
authors.forename: Ellinor
authors.initials: E
authors.lastname: Kenne
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
authors.forename: Guillem
authors.initials: G
authors.lastname: Genové
authors.forename: Pierre
authors.initials: P
authors.lastname: Rotzius
authors.forename: Einar E
authors.initials: EE
authors.lastname: Eriksson
authors.forename: Lennart
authors.initials: L
authors.lastname: Lindbom
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D007797:Laminin / Q000172:deficiency* / Q000378:metabolism; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport
chemical_list: C501370:Lama4 protein, mouse; D007797:Laminin; D020033:Protein Isoforms; C097043:laminin alpha5