A vitellogenic-like carboxypeptidase expressed by human macrophages is localized in endoplasmic reticulum and membrane ruffles.
Carboxypeptidase, vitellogenic-like (CPVL) is a serine carboxypeptidase of unknown function that was first characterized in human macrophages. Initial studies suggested that CPVL is largely restricted to the monocytic lineage, although it may also be expressed by cells outside the immune system. Here, we use a new monoclonal antibody to characterize the properties and localization of CPVL in human macrophages to elucidate a possible function for the protease. CPVL is up-regulated during the maturation of monocytes (MO) to macrophages, although the protein can be seen in both. In primary macrophages, CPVL is glycosylated with high mannose residues and colocalizes with markers for endoplasmic reticulum, while in MO it is more disperse and less clearly associated with endoplasmic reticulum. CPVL is highly expressed in lamellipodia and membrane ruffles, which also concentrate markers of the secretory pathway (MIP-1alpha and tumour necrosis factor-alpha) and major histocompatibility complex (MHC) class I and II molecules. CPVL can be seen on early latex bead and Candida albicans phagosomes, but it is not retained in the maturing phagosome, unlike MHC class I/II. CPVL has a mixed cytosolic and membrane-associated localization but is not detectable on the outer plasma membrane. We propose that CPVL may be involved in antigen processing, the secretory pathway and/or in actin remodelling and lamellipodium formation.
Harris
James
J
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. jimharris@salud.unm.edu
Schwinn
Nicole
N
Mahoney
James A
JA
Lin
Hsi-Hsien
HH
Shaw
Michael
M
Howard
Chris J
CJ
da Silva
Rosangela P
RP
Gordon
Siamon
S
D000911:Antibodies, Monoclonal / Q000032:analysis / Q000302:isolation & purification; D017951:Antigen Presentation; D015153:Blotting, Western / Q000379:methods; D002268:Carboxypeptidases / Q000032:analysis* / Q000302:isolation & purification; D002454:Cell Differentiation; D002462:Cell Membrane / Q000737:chemistry* / Q000648:ultrastructure; D003600:Cytosol / Q000737:chemistry* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000648:ultrastructure; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry; D008264:Macrophages / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009000:Monocytes / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D010587:Phagocytosis; D011554:Pseudopodia / Q000737:chemistry / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D002268:Carboxypeptidases; C508747:CPVL protein, human