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Abstract

Introduction: Integrins are crucial for migration of leukocytes through endothelium in systemic inflammatory response syndrome (SIRS). Some reports suggested integrins independent mechanisms appeared to regulate the migration of leukocytes through inflammatory extracellular matrix. We identified the up-regulation of discoidin domain receptor 1 (DDR1) in the genes profile of activated neutrophils by cDNA arrray. DDR1 has two major isoforms, DDR1a and DDR1b, which are a receptor tyrosine kinase activated by collagen. Methods: We extracted human leukocytes from bloods of healthy donors for in-vitro assay. The expression of DDR1 mRNAs and proteins in leukocytes was examined by Northern blotting, RT-PCR, IP-Western Blotting, In-situ hybridization in a various condition. DDR1a- or DDR1b -overexpressing THP-1 cells were analyzed the migration and adhesion with or without collagen. Results: Isolated neutrophils and PBMC expressed DDR1 mRNA and protein that was increased by LPS, TNF alpha or IL-1 beta, but not by IFN gamma. Infiltrating leukocytes expressed DDR1 mRNA in human stromal tissues by in-situ hybridization. DDR-1a and -1b expressing THP-1 cells resulted in increased adherence to collagen-coated plates in a beta1-integrin independent manner. DDR1a-, but not DDR1b-, overexpressing cells exhibited marked pseudopod extension and migrated successfully through three-dimensional collagen lattices. Conclusions: The interaction of DDR1a with stromal collagen enhanced leukocytes migration in inflammatory tissue microenvironment. Regulation of DDR1a might contribute to host defense in SIRS.