Differential regulation of aminopeptidase N (CD13) by transendothelial migration and cytokines on human eosinophils.
Aminopeptidase N (CD13) is a cell surface metalloprotease involved in growth regulation, tumor invasion, and down-regulation of regulatory peptides. CD13 expression on eosinophils in bronchoalveolar lavage (BAL) of asthmatics 10 minutes and 18 hours after segmental allergen provocation was significantly increased (+225% to +294%) compared to blood eosinophils. In vitro CD13 expression could be induced on blood eosinophils by transendothelial migration of the cells across interlenkin (IL) 1beta-activated human umbilical cord vein endothelial cells (HUVECs) as well as by the exposure to the cytokines IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF). The cytokines GM-CSF and IL-5 were significantly less effective in inducing CD13 compared to IL-3. The IL-3-induced expression of CD13 was decreased in the presence of the protein-synthesis inhibitor cycloheximide (-8.8%). Moreover, blocking of CD13 by the protease inhibitors actinonin and bestatin significantly enhanced migration (+40.0% to +80.0%) of eosinophils across HUVEC monolayers. In summary, the data suggest that CD13 is regulated both by the process of transmigration and by the cytokine IL-3. Further, CD13 itself seems to be involved in the process of eosinophil transmigration. aminopeptidase Nendothelial cellseosinophilsinterleukin-3interleukin-5transendothelial migration
Braun
Ruedi K
RK
Department of Pneumology, Allergy, and Immunology, Medical Clinic IV, Friedrich Schiller University, Jena, Germany.
Foerster
Martin
M
Workalemahu
Grefachew
G
Haefner
Daniela
D
Kroegel
Claus
C
Walker
Christoph
C
D000328:Adult; D001249:Asthma / Q000201:enzymology* / Q000276:immunology; D001985:Bronchial Provocation Tests; D018893:Bronchoalveolar Lavage; D018826:CD13 Antigens / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects* / Q000201:enzymology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D008297:Male; D014471:Umbilical Veins; D015854:Up-Regulation
D016207:Cytokines; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D018826:CD13 Antigens