Elevated neutrophil membrane expression of proteinase 3 is dependent upon CD177 expression.
Proteinase 3 (PR3) is a major autoantigen in anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV), and the proportion of neutrophils expressing PR3 on their membrane (mPR3+) is increased in AASV. We have shown recently that mPR3 and CD177 are expressed on the same cells in healthy individuals. In this study we try to elucidate mechanisms behind the increased mPR3 expression in AASV and its relationship to CD177. All neutrophils in all individuals were either double-positive or double-negative for mPR3 and CD177. The proportion of double-positive neutrophils was increased significantly in AASV and systemic lupus erythematosus patients. The proportion of mPR3+/CD177+ cells was not correlated to general inflammation, renal function, age, sex, drug treatment and levels of circulating PR3. AASV patients had normal levels of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Pro-PR3 was found to constitute 10% of circulating PR3 but none of the mPR3. We found increased mRNA levels of both PR3 and CD177 in AASV, but they did not correlate with the proportion of double-positive cells. In cells sorted based on membrane expression, CD177-mRNA was several-fold higher in mPR3+ cells. When exogenous PR3 was added to CD177-transfected U937 cells, only CD177+ cells bound PR3 to their membrane. In conclusion, the increased membrane expression of PR3 found in AASV is not linked directly to circulating PR3 or PR3 gene transcription, but is dependent upon CD177 expression and correlated with the transcription of the CD177 gene.
Abdgawad
M
M
Department of Nephrology, Lund University, Lund, Sweden. Mohamed.Abdgawad@med.lu.se
Gunnarsson
L
L
Bengtsson
A A
AA
Geborek
P
P
Nilsson
L
L
Segelmark
M
M
Hellmark
T
T
D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood / Q000201:enzymology* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000201:enzymology / Q000276:immunology; D001782:Blood Donors; D002462:Cell Membrane / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016030:Kidney Transplantation; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000201:enzymology / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D053146:Myeloblastin / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D020298:U937 Cells / Q000187:drug effects / Q000201:enzymology
C407242:CD177 protein, human; D058851:GPI-Linked Proteins; D007519:Isoantigens; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D053146:Myeloblastin