Secretory low-molecular-weight phospholipases A(2) and their specific receptor in bile ducts of patients with intrahepatic calculi: Factors of chronic proliferative cholangitis

Citation
J. Shoda et al., Secretory low-molecular-weight phospholipases A(2) and their specific receptor in bile ducts of patients with intrahepatic calculi: Factors of chronic proliferative cholangitis, HEPATOLOGY, 29(4), 1999, pp. 1026-1036
Citations number
74
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
HEPATOLOGY
ISSN journal
0270-9139 → ACNP
Volume
29
Issue
4
Year of publication
1999
Pages
1026 - 1036
Database
ISI
SICI code
0270-9139(199904)29:4<1026:SLPAAT>2.0.ZU;2-H
Abstract
Intrahepatic calculi is characterized by an intractable course and frequent recurrences, requiring multiple operative interventions. Chronic prolifera tive cholangitis, an active and long-standing inflammation of the stone-con taining bile ducts with the hyperplasia of epithelia and the proliferation of the duct-associated mucus glands, may underlie the complex nature of the disease. In terms of the pathophysiology, interest has been focused on the role of secretory low-molecular-weight phospholipases A(2) (sPLA(2)s) as i nflammatory mediators or factors modulating cell functions via their specif ic sPLA(2)-receptor, and also on the production and secretion of altered mu cin molecules from the inflamed bile ducts. In search of factors involving chronic proliferative cholangitis, the sPLA(2) isoforms in the bile such as the pancreatic-type sPLA(2) (group IB sPLA(2)) and the arthritic-type sPLA (2) (group IIA sPLA(2)), were assayed to correlate protein masses of the sP LA(2)s with alterations in biliary composition. Furthermore, the steady-sta te messenger RNA (mRNA) levels of the sPLA(2)s, the membrane-bound sPLA(2)- receptor, cystic fibrosis transmembrane conductance regulator (CFTR), and m ucin core polypeptide (MUC) genes in the bile ducts were assayed by reverse -transcriptase polymerase chain reaction (RT-PCR), Immuno-reactive sPLA(2)- IB and sPLA(2)-IIA levels it ere significantly higher in the bile from the stone-containing hepatic ducts (2315 +/- 677 for sPLA(2)-IB; 281 +/- 42 for sPLA(2)-IIA ng/dL, mean +/- SEM; n = 20) than in the ductal bile from gall bladder stone patients (609 +/- 92, P < .01; 22 +/- 2, P < .01; n = 24). Th e increased sPLA(2) levels were associated with a concomitant increase in l ysophosphatidylcholine, prostaglandin E-2 (PGE(2)), and total mucin concent rations. The affected bile ducts showed an increased mRNA level of sPLA(2)- IB and sPLA(2)-IIA compared with the ducts from control subjects, in whom t he mRNAs of the sPLA(2)-receptor and other sPLA(2) isoforms, such as groups V and X sPLA(2)s, were coincidently expressed. Reflecting the: increased a mounts of total biliary mucins, the affected ducts showed an increase in mR NA levels of CFTR as well as MUC2, MUC3, MUC5AC, MUC5B, and MUC6 compared w ith the ducts from control subjects. In intrahepatic calculi, an enhanced e xpression of the sPLA(2)s and their possible cross-talk via sPLA(2)-recepto r may be of pathophysiological significance for the chronic proliferative c holangitis, in association with the enhanced CFTR expression and the altera tions in mucin gene expression in the bile ducts, probably through potentia ting arachidonate metabolism with associated biliary alterations favoring g rowth of preexisting stones and even further progressions.