Sorting of neutrophil-specific granule protein human cathelicidin, hCAP-18, when constitutively expressed in myeloid cells.
Neutrophil granulocytes carry storage organelles, e.g., azurophil and specific granules. Poorly understood are the mechanisms for retrieval from constitutive secretion followed by sorting for storage. Therefore, we asked whether the specific granule protein human cathelicidin (hCAP-18) could be sorted for storage in other granules when the biosynthetic window is widened to allow this. We observed that hCAP-18 was targeted for storage in lysosome-related organelles when expressed constitutively in the rat basophilic leukemia and the mouse promyelocytic (MPRO) cell lines. In addition, premature release of the antibiotic C-terminal peptide LL-37 was observed. Retention of hCAP-18 was diminished by induction of differentiation of MPRO cells. In conclusion, a specific granule protein with native conformation may be sorted for storage in lysosome-related organelles of myeloid cells and converted prematurely to a supposedly biologically active form.
Bülow
Elinor
E
Department of Hematology, BMC, C14, Lund University, S-221 84 Lund, Sweden. elinor.bulow@hematologi.lu.se
Bengtsson
Niklas
N
Calafat
Jero
J
Gullberg
Urban
U
Olsson
Inge
I
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D054804:Cathelicidins; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000648:ultrastructure; D008247:Lysosomes / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D022423:Myeloid Cells / Q000378:metabolism* / Q000648:ultrastructure; D023461:Myeloid Progenitor Cells / Q000378:metabolism; D009504:Neutrophils / Q000737:chemistry; D021381:Protein Transport; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins