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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1859-1866.
Prepublished online as a Blood First Edition Paper on June 1, 2004; DOI 10.1182/blood-2004-01-0396.
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PHAGOCYTES
An endothelial laminin isoform, laminin 8 ( 4 1 1), is secreted by blood neutrophils, promotes neutrophil migration and extravasation, and protects neutrophils from apoptosis
Zenebech Wondimu,
Tarekegn Geberhiwot,
Sulev Ingerpuu,
Erkki Juronen,
Xun Xie,
Lennart Lindbom,
Masayuki Doi,
Jarkko Kortesmaa,
Jill Thyboll,
Karl Tryggvason,
Bengt Fadeel, and
Manuel Patarroyo
From the Department of Odontology, the Microbiology and Tumorbiology Center, the Department of Physiology and Pharmacology, the Department of Medical Biochemistry and Biophysics, and the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; and the Institute of Molecular and Cell Biology, and the Institute of General and Molecular Pathology, University of Tartu, Tartu, Estonia.
During extravasation, neutrophils migrate through the perivascular basement membrane (BM), a specialized extracellular matrix rich in laminins. Laminins 8 (LN-8) ( 4 1 1) and 10 (LN-10) (511) 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 4 (LN4) chain, that neutrophils contain and secrete LN-8, and that this endogenous laminin contributes to chemoattractant-induced, M2-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) (111) via M2-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 LN4-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.
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