Heterogeneity of the human exocrine pancreas: Antidigestive enzyme antibody and lectin binding

Abstract

We have previously reported the existance of fundamental heterogeneity of the exocrine pancreas in animals; binding of specific anti-digestive enzyme antibodies and lectins to intact pancreatic tissue and isolated acinar cells of rabbit and rat revealed highly heterogenous patterns of distribution of acinar cell digestive enzyme contents (J Histochem Cytochem 1995;44:215 and Gastroenterol 1997;112:A435). Aim: To determine if the adult human pancreas is heterogeneous. Methods: Areas of normal pancreas were obtained without alteration of the surgical procedure from the margins of resected specimens in 5 patients ages 56-76, two with serous cystadenoma, and three with pancreatic cancer. Tissue was fixed and sectioned by standard methods. Sections were permeabilized with saponin, and treated with commerciallyavailable anti-digestive enzyme antibodies employed singly or in pairs directed against amylase, lipase, chymotrypsin and trypsinogen, or with a panel of lectins. Vizualization was by both diaminobenzidine and fluoresence with FITC or Texas red. Routine hematoxylin and eosin staining was employed to ascertain tissue integrity, morphology and absence of pathology. Results: The human pancreas was distinctly heterogeneous at the morphological level as demonstrated by antidigestive enzyme antibody binding. Several patterns of heterogeneity were readily discerned: first, a pattern unique to the human wherein whole lobules were clearly labeled by one of a pair of antibodies -highly lipase-, chymotrypsinand amylasedominant lobules were noted to contrast with other areas where enzymes were co-localized. Second, an autumn leaves-type pattern was noted in which individual acini were found to contain either amylase or lipase predominantly. A third pattern wherein individual acinar cells differed in digestive enzyme content from neighboring cells within the same acinus, and a fourth pattern of anti-digestive enzyme antibody staining in halos of lipase-rich acinar cells surrounding the islets of Langerhans were also noted. Lectins LTL and UEA also strongly showed lobular patterns of heterogeneous binding. Lectins HPA, ACL, WFA, SBA and SWGA showed heterogeneous patterns from cell-tocell in the zymogen granule region. Lectin PHA showed distinct halos of acinar cells surrounding the islets. Numerous species differences in the patterns of heterogeneity were found; the human gland appeared even more broadly heterogeneous than rabbit or rat, and showed an extensive lobular pattern not seen as readily in the other species. Conclusion: The exocrine pancreas in the human adult is fundamentally heterogeneous with respect to the distribution of individual digestive enzyme species within acinar cells, acini, and pancreatic lobules. The heterogeneous interand intra-acinar patterns as well as the peri-insular halos have been found in all species examined; the highly lobular pattern for lipase, amylase and chymotrypsin is, to date, unique to the human.