Impaired chemotaxis and cell adhesion due to decrease in several cell-surface receptors in cathepsin E-deficient macrophages

• Published in: Journal of biochemistry (Tokyo) Vol. 145; no. 5; pp. 565 - 573
• Main Authors: Tsukuba, Takayuki, Yanagawa, Michiyo, Okamoto, Kuniaki, Okamoto, Yoshiko, Yasuda, Yoshiyuki, Nakayama, Keiichi I, Kadowaki, Tomoko, Yamamoto, Kenji
• Format: Journal Article
• Language: English
• Published: England Japanese Biochemical Society 01.05.2009; Oxford University Press
• Subjects: Animals; aspartic proteinase; cathepsin E; Cathepsin E - deficiency; Cathepsin E - metabolism; cell adhesion; Cell Adhesion - drug effects; Cell Count; chemotaxis; Chemotaxis - drug effects; Dextrans - metabolism; Endocytosis - drug effects; Fibronectins - metabolism; Flow Cytometry; Fluorescein-5-isothiocyanate - analogs & derivatives; Fluorescein-5-isothiocyanate - metabolism; knockout; Lysosomal Membrane Proteins - metabolism; Lysosomal-Associated Membrane Protein 2 - metabolism; macrophages; Macrophages, Peritoneal - cytology; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - metabolism; Mice; N-Formylmethionine Leucyl-Phenylalanine - analogs & derivatives; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Receptors, Cell Surface - metabolism; Thioglycolates - pharmacology; knockout; macrophages; cathepsin E; cell adhesion; aspartic proteinase; chemotaxis
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/jb/mvp016

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.