Helicobacter pylori infection and short-term intake of low-dose aspirin have different effects on alpha-1 antitrypsin/alpha-1 peptidase inhibitor (alpha1-PI) levels in antral mucosa and peripheral blood.
OBJECTIVE
Alpha-1 protease inhibitor (alpha1-PI) is the major circulating serine protease inhibitor. The purpose of the study was to investigate alpha1-PI expression in gastroduodenal mucosa and blood with respect to two major etiological risk factors for gastroduodenal diseases, Helicobacter pylori infection and intake of low-dose aspirin.


METHODS
Twenty volunteers (H. pylori-positive and -negative: n=10) received 2 x 50 mg aspirin/day for 7 days. H. pylori-positive subjects underwent eradication therapy and repeated the protocol. Blood and tissue samples were obtained on days 0, 1, 3 and 7; alpha1-PI levels were determined by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and analyzed for histopathological findings.


RESULTS
Mucosal alpha1-PI expression was between 30 and 75 pg/10 microg total protein in H. pylori-negative subjects, and found to be similar in antral, corpus and duodenal mucosa. In H. pylori-infected subjects, alpha1-PI levels were significantly increased in the antrum (mean: 111 versus 37.4 pg/10 microg protein; p=0.019), whereas corresponding levels in the corpus, duodenum and sera were unchanged. Alpha-1-PI transcript levels were similarly induced in H. pylori-infected subjects (0.13+/-0.15 versus 0.027+/-0.043 a.u. (arbitrary units), p=0.018). Immunohistochemistry demonstrated that infiltrating immune cells and antral surface epithelium contributed to elevated alpha1-PI expression in H. pylori-infected subjects. The concomitant use of low-dose aspirin did not change mucosal alpha1-PI levels, but led to a 2-fold increase in alpha1-PI levels in sera independently of the H. pylori status (p<0.009).


CONCLUSIONS
Antral alpha1-PI expression is specifically induced by H. pylori infection, suggesting a pathophysiological role of this protease inhibitor in the upper gastrointestinal tract, whereas low-dose aspirin led to an increase in systemic alpha1-PI levels.
Wex
Thomas
T
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany. thomas.wex@medizin.uni-magdeburg.de
Kuester
Doerthe
D
Vieth
Michael
M
Treiber
Gerhard
G
Krieg
Anja
A
Roessner
Albert
A
Malfertheiner
Peter
P
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism / Q000382:microbiology; D015870:Gene Expression / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D016481:Helicobacter Infections / Q000188:drug therapy / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D011706:Pyloric Antrum / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000515:alpha 1-Antitrypsin; D001241:Aspirin