The fate of leukocytes in a tissue microenvironment is strongly influenced by up- or down-regulation of cell-surface receptor expression, and subsequent interaction of the receptors with their ligands. These ligands include a wide range of agents secreted at the sites and the components of the extracellular matrix (ECM). Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase whose ligand is collagen. We recently detected, for the first time, that peripheral blood mononuclear cells and neutrophils were induced to express DDR1. Functionally, overexpression of the DDR1a isoform in the human monocytic leukemic cell line, THP-1, increased adherence and marked pseudopod formation on collagen-coated plates in a 1-integrin independent manner, and promoted the migration through three-dimensional collagen lattices. Consequently, we have proposed that the interaction of DDR1a 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.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010258-06
Application #
6762715
Study Section
(LMI)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Matsuyama, Wataru; Watanabe, Masaki; Shirahama, Yuko et al. (2005) Activation of discoidin domain receptor 1 on CD14-positive bronchoalveolar lavage fluid cells induces chemokine production in idiopathic pulmonary fibrosis. J Immunol 174:6490-8
Yoshimura, Teizo; Matsuyama, Wataru; Kamohara, Hidenobu (2005) Discoidin domain receptor 1: a new class of receptor regulating leukocyte-collagen interaction. Immunol Res 31:219-30
Cho, Hyosun; Lasco, Todd M; Allen, Shannon Sedberry et al. (2005) Recombinant guinea pig tumor necrosis factor alpha stimulates the expression of interleukin-12 and the inhibition of Mycobacterium tuberculosis growth in macrophages. Infect Immun 73:1367-76
Calvo, Charles-Felix; Amigou, Edwige; Tence, Martine et al. (2005) Albumin stimulates monocyte chemotactic protein-1 expression in rat embryonic mixed brain cells. J Neurosci Res 80:707-14
Galligan, Carole L; Matsuyama, Wataru; Matsukawa, Akihiro et al. (2004) Up-regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis. Arthritis Rheum 50:1806-14
Matsuyama, Wataru; Wang, Lihua; Farrar, William L et al. (2004) Activation of discoidin domain receptor 1 isoform b with collagen up-regulates chemokine production in human macrophages: role of p38 mitogen-activated protein kinase and NF-kappa B. J Immunol 172:2332-40
Kamohara, Hidenobu; Matsuyama, Wataru; Shimozato, Osamu et al. (2004) Regulation of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor expression in human neutrophils. Immunology 111:186-94
Jeevan, Amminikutty; Yoshimura, Teizo; Lee, Kyeong Eun et al. (2003) Differential expression of gamma interferon mRNA induced by attenuated and virulent Mycobacterium tuberculosis in guinea pig cells after Mycobacterium bovis BCG vaccination. Infect Immun 71:354-64
Lasco, Todd M; Yamamoto, Toshiko; Yoshimura, Teizo et al. (2003) Effect of Mycobacterium bovis BCG vaccination on Mycobacterium-specific cellular proliferation and tumor necrosis factor alpha production from distinct guinea pig leukocyte populations. Infect Immun 71:7035-42
Matsuyama, Wataru; Kamohara, Hidenobu; Galligan, Carole et al. (2003) Interaction of discoidin domain receptor 1 isoform b (DDR1b) with collagen activates p38 mitogen-activated protein kinase and promotes differentiation of macrophages. FASEB J 17:1286-8

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