Increased expression of the secretory leukocyte proteinase inhibitor in Wegener's granulomatosis.
The secretory leucocyte proteinase inhibitor (SLPI) is a low molecular weight, tissue-specific inhibitor of proteases, such as elastase and cathepsin G. It is the major local protease inhibitor in the upper airways. Proteinase 3, the main autoantigen in Wegener's granulomatosis (WG), can degrade SLPI proteolytically. In addition, SLPI is sensitive to oxidative inactivation by myeloperoxidase-generated free oxygen radicals. SLPI also has an antimicrobial capacity that can be of interest, as infection is considered to play a role in the pathogenesis of WG. This study focuses on SLPI expression in patients suffering from WG, something that to our knowledge has not been explored hitherto. Serum samples and nasal biopsies were obtained from 12 Swedish WG patients, while buffy coats were obtained from 33 American WG patients. SLPI levels in serum were measured by means of ELISA and the protein was detected by means of immunohistochemistry in nasal biopsies. mRNA expression was studied by means of in situ hybridization on nasal biopsies and RT-PCR on leucocytes. IL-6 or ESR were measured as markers of inflammatory activity. Cystatin C or creatinine was measured as a marker of renal filtration. White blood cell counts were registered. In serum, we found close to normal SLPI levels, without any correlation to IL-6. Two patients had greatly elevated values, both of them suffering from severe renal engagement. Strong SLPI mRNA expression was found in nasal biopsies. RT-PCR on leucocyte mRNA showed normal or greatly elevated expression of SLPI mRNA, correlating with disease activity. Leukocyte SLPI expression seems to be up-regulated in active WG. Serum levels were measured in a small number of patients and were found to be close to normal. Lack of correlation to the acute phase response indicates a specific regulation. This might be linked to an altered protease/antiprotease balance. These findings could indicate that SLPI locally participates in the anti-inflammatory and perhaps antimicrobial response in WG.
Ohlsson
S
S
Department of Nephrology, Lund University Hospital, Lund, Sweden. Sophie.Ohlsson@njur.lu.se
Falk
R
R
Yang
J J
JJ
Ohlsson
K
K
Segelmark
M
M
Wieslander
J
J
D000704:Analysis of Variance; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D014890:Granulomatosis with Polyangiitis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007962:Leukocytes / Q000737:chemistry; D009297:Nasal Mucosa / Q000201:enzymology; D010196:Pancreatic Elastase / Q000032:analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D053481:Secretory Leukocyte Peptidase Inhibitor
D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012333:RNA, Messenger; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D010196:Pancreatic Elastase