title: An endothelial laminin isoform, laminin 8 (alpha4beta1gamma1), is secreted by blood neutrophils, promotes neutrophil migration and extravasation, and protects neutrophils from apoptosis.
abstract: During extravasation, neutrophils migrate through the perivascular basement membrane (BM), a specialized extracellular matrix rich in laminins. Laminins 8 (LN-8) (alpha4beta1gamma1) and 10 (LN-10) (alpha5beta1gamma1) are major components of the endothelial BM, but expression, recognition, and use of these laminin isoforms by neutrophils are poorly understood. In the present study, we provide evidence, using a panel of novel monoclonal antibodies against human laminin alpha4 (LNalpha4) chain, that neutrophils contain and secrete LN-8, and that this endogenous laminin contributes to chemoattractant-induced, alphaMbeta2-integrin-dependent neutrophil migration through albumin-coated filters. Phorbol ester-stimulated neutrophils adhered to recombinant human (rh) LN-8, rhLN-10, and mouse LN-1 (mLN-1) (alpha1beta1gamma1) via alphaMbeta2-integrin, and these laminin isoforms strongly promoted chemoattractant-induced neutrophil migration via the same integrin. However, only rhLN-8 enhanced the spontaneous migration. In addition, recruitment of neutrophils into the peritoneum following an inflammatory stimulus was impaired in LNalpha4-deficient mice. rhLN-8 also protected isolated neutrophils from spontaneous apoptosis. This study is the first to identify a specific laminin isoform in neutrophils and provides evidence for the role of LN-8 in the adhesion, migration, extravasation, and survival of these cells.
authors.affiliation: Department of Odontology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Zenebech
authors.initials: Z
authors.lastname: Wondimu
authors.forename: Tarekegn
authors.initials: T
authors.lastname: Geberhiwot
authors.forename: Sulev
authors.initials: S
authors.lastname: Ingerpuu
authors.forename: Erkki
authors.initials: E
authors.lastname: Juronen
authors.forename: Xun
authors.initials: X
authors.lastname: Xie
authors.forename: Lennart
authors.initials: L
authors.lastname: Lindbom
authors.forename: Masayuki
authors.initials: M
authors.lastname: Doi
authors.forename: Jarkko
authors.initials: J
authors.lastname: Kortesmaa
authors.forename: Jill
authors.initials: J
authors.lastname: Thyboll
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
authors.forename: Manuel
authors.initials: M
authors.lastname: Patarroyo
mesh_terms: D016604:Aflatoxin B1; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D002364:Caseins / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement; D042783:Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D012709:Serum Albumin
chemical_list: D000911:Antibodies, Monoclonal; D002364:Caseins; D016023:Integrins; C501369:LAMA4 protein, human; C501370:Lama4 protein, mouse; D007797:Laminin; D010446:Peptide Fragments; D020033:Protein Isoforms; D012709:Serum Albumin; C052669:aflatoxin B1-bovine serum albumin; C110308:laminin 8; C018135:proteose-peptone; D016604:Aflatoxin B1