Impaired chemotaxis and cell adhesion due to decrease in several cell-surface receptors in cathepsin E-deficient macrophages.
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 beta(2)) and CD 29 (integrin beta(1)) 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.
Tsukuba
Takayuki
T
Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. tsuta@nagasaki-u.ac.jp
Yanagawa
Michiyo
M
Okamoto
Kuniaki
K
Okamoto
Yoshiko
Y
Yasuda
Yoshiyuki
Y
Nakayama
Keiichi I
KI
Kadowaki
Tomoko
T
Yamamoto
Kenji
K
D000818:Animals; D020059:Cathepsin E / Q000172:deficiency* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D002633:Chemotaxis / Q000187:drug effects; D003911:Dextrans / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013864:Thioglycolates / Q000494:pharmacology; D052118:Lysosomal-Associated Membrane Protein 1
D020059:Cathepsin E; D003911:Dextrans; D005353:Fibronectins; D016650:Fluorescein-5-isothiocyanate; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011956:Receptors, Cell Surface; D013864:Thioglycolates; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C015219:fluorescein isothiocyanate dextran; C042205:methionyl-leucyl-phenylalanine