Journal of Biochemistry Advance Access originally published online on January 27, 2009
Journal of Biochemistry 2009 145(5):565-573; doi:10.1093/jb/mvp016
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Impaired chemotaxis and cell adhesion due to decrease in several cell-surface receptors in cathepsin E-deficient macrophages
1Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588; 2Department of Fixed Prosthodontics, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582; 3Department of Biochemistry, Daiichi University College of Pharmaceutical Sciences, Fukuoka 815-8511; 4Division of Clinical Cariology and Endodontology, Department of Oral Rehabilitation, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido, 061-0293; 5Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582; 6Pharmacology, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582; and 7Proteolysis Research Laboratory, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
*To whom correspondence should be addressed. Tel: +81 95 819 7652, Fax: +81 95 819 7655, E-mail: tsuta{at}nagasaki-u.ac.jp
Received November 26, 2008; Accepted January 9, 2009
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Abstract |
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Cathepsin E is an endo-lysosomal aspartic proteinase exclusively present in immune system cells. Previous studies have shown that cathepsin E-deficient (CatE–/–) mice display aberrant immune responses such as atopic dermatitis and higher susceptibility to bacterial infection. However, the mechanisms underlying abnormal immune responses induced by cathepsin E deficiency are still unclear. In this study, we found that the cell-surface levels of chemotactic receptors, including chemokine receptor (CCR)-2 and N-formyl peptide receptors (FPRs), were clearly diminished in CatE–/–macrophages compared with those in wild-type cells. Consistently, chemotaxis of CatE–/–macrophages to MCP-1 and N-formyl-methionyl-leucyl-phenylalanine was also decreased. Similar to the chemotactic receptors, the surface expressions of the adhesion receptors CD18 (integrin β2) and CD 29 (integrin β1) in CatE–/– macrophages were significantly decreased, thereby reducing cell attachment of CatE–/– macrophages. These results indicate that the defects in chemotaxis and cell adhesion are likely to be involved in the imperfect function of CatE–/–macrophages.
Key Words: aspartic proteinase, cathepsin E, knockout, macrophages, chemotaxis, cell adhesion
Abbreviations: CatE–/–, cathepsin E-deficient; CCR-2, chemokine receptor; FITC, fluorescein isothiocyanate; FPRs, N-formyl peptide receptors; LAMP, lysosome-associated membrane protein; MCP, monocyte chemoattractant protein; PBS, phosphate buffered saline; PE, phycoerythin; TLRs, toll-like receptors