Discoidin domain receptor 1 isoform-a (DDR1alpha) promotes migration of leukocytes in three-dimensional collagen lattices.

H. Kamohara, S. Yamashiro, C. Galligan, T. Yoshimura

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Although integrins are crucial for migration of leukocytes through endothelium, integrin-independent mechanisms appear to take over and mediate the migration of leukocytes through extracellular matrix (ECM) in a three-dimensional tissue microenvironment. Discoidin domain receptor (DDR) 1 is a receptor tyrosine kinase activated by collagen, the most abundant ECM protein. In the present study, we detected that peripheral blood mononuclear cells (PBMC) and polymorphonuclear neutrophils were induced to express DDR1 after incubation in RPMI 1640. The expression level of DDR1 in PBMC was increased further by stimulation with tumor necrosis factor-alpha, interleukin-1beta, granulocyte-macrophage colony-stimulating factor, lipopolysaccharide, or phytohemagglutinin, but not with interferon-gamma. In vivo, DDR1 mRNA was detectable in mononuclear leukocytes infiltrating human renal tumor tissue. Among three DDR1 isoforms, DDR1alpha was the major transcript in leukocytes. Functionally, overexpression of either DDR1alpha or DDR1beta in THP-1 cells resulted in increased adherence to collagen-coated plates in a beta1-integrin independent manner. However, only DDR1alpha-, but not DDR1beta-, overexpressing cells exhibited marked pseudopod extension and migrated successfully through three-dimensional collagen lattices. Consequently, we propose that the interaction of DDR1alpha with collagen of the ECM results in a requisite intracellular signaling that enables leukocytes to migrate in a tissue microenvironment and participate in host defense.

Original languageEnglish
Pages (from-to)2724-2726
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume15
Issue number14
Publication statusPublished - Dec 2001
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this