EXPRESSION OF HEAT-SHOCK PROTEINS IN CHRONIC-PANCREATITIS - PROTECTIVE OR PATHOGENIC ROLES

The tissue-distributions of heat shock proteins (HSP) identified by mo noclonal antibodies ML-30, TB-78, GA-Str7-1, and MAB 72/73 have been e xamined in formalin-fixed and paraffin wax-embedded tissues from 10 no rmal pancreatic specimens and 92 cases of chronic pancreatitis. The ch ronic pancreatitis cases were divided by probable etiology into alcoho l-related, postacute pancreatitis, or idiopathic. The HSP identified b y ML-30 and CA-Str7-1 were constitutively expressed, with a regional d istribution, by duct and ductular epithelial cells in all normal pancr eatic tissues. The HSP detected by ML-30 were expressed uniformly thro ughout the cytoplasm of the majority of ductular epithelial cells in a ll cases of chronic pancreatitis, irrespective of suspected etiology, and in the ducts of all but two cases of alcohol-associated chronic pa ncreatitis. The HSP defined by CA-Str7-1 were identified in the majori ty of duct or ductular epithelial cells in most of the cases of chroni c pancreatitis, although possible differential expression was observed with respect to etiology tie, there seemed to be less HSP in cases of postalcohol pancreatitis). The HSP identified by TB-78 were not const itutively expressed by normal pancreatic tissues but were found in a f ew scattered epithelial cells in two of these cases. However, signific ant expression of these HSP were observed in most epithelial cells in a population of cases regarded as either alcohol-associated (0.05 > p > 0.02) or postacute chronic pancreatitis (0.01 > p > 0.001). The HSP identified by monoclonal antibody MAB 72/73 were either not demonstrab le or were expressed at very low levels in both the normal and inflame d pancreatic tissues. Expression of the four groups of HSP molecules a ppeared to be differentially regulated both in normal pancreatic and i n chronic pancreatitis tissues. These differences in expression may in dicate different functions in normal tissues, with either a protective or a pathogenic role for these proteins in the diseased state. Our cu rrent findings support the hypothesis that expression of certain HSP, particularly those identified by TB-78, may be involved in the pathoge nesis of distinct subtypes of chronic pancreatitis. Our data do not su ggest that HSP are the primary targets of immune-mediated cytotoxic ac tivity; nevertheless, enhanced expression of these molecules by pancre atic ductular epithelial cells does provide an environment in which in creased amounts of endogenous intracellular peptides may be transporte d to the cell surface, thereby becoming potential targets of immune-su rveillance and cell-mediated cytotoxicity. Conversely, HSP may play a protective role in such a manner that selected groups of pancreatic du ctular epithelial cells withstand cytotoxic damage of chemical, metabo lic, or immune origin, and for significantly increased periods of time than they would otherwise, HSP thereby conserve a population of ''res erve'' epithelial cells from which pancreatic regeneration might occur . identification of distinct pathogenic groups, defined according to p recise immunohistochemical criteria, might provide the basis of a func tional assessment and hence allow development of biologically appropri ate strategies for managing individual patients with chronic pancreati tis.