Skip to main content
NCBI home page
Journal of Anatomy logoLink to Journal of Anatomy
. 1996 Oct;189(Pt 2):303–313.

Human gastric intrinsic factor expression is not restricted to parietal cells.

T A Howard 1, D N Misra 1, M Grove 1, M J Becich 1, J S Shao 1, M Gordon 1, D H Alpers 1
PMCID: PMC1167747  PMID: 8886952

Abstract

Gastric parietal cells have been accepted as the only site of intrinsic factor production in the human stomach. In animals, however, intrinsic factor has been localised to various other cell types of foregut origin, including chief and enteroendocrine cells in gastric mucosa, and duct cells from salivary glands and pancreas. The availability of recombinant human intrinsic factor has led to production of high titre, monospecific antiserum which was used to reexamine the distribution and subcellular localisation of intrinsic factor in the human stomach. Immunolight microscopy revealed that most positively stained cells were gastric parietal cells, but at the margins of the anatomical regions (e.g. cardia/fundus, body/antrum) clusters of gastric chief cells and individual enteroendocrine cells were found to contain intrinsic factor. Immunoelectron microscopy demonstrated the highest antigen density on endocytic and apical membranes of parietal cells. Exocrine secretory granules of a subpopulation of chief cells, the secretory granules of some enteroendocrine cells, and the plasma membranes and smooth vesicles of endothelial cells of the lamina propria capillaries underlying enteroendocrine cells were also positive for the antigen. Labelling in all cells was specific, as it was abolished by preabsorption of the antisera with purified recombinant human intrinsic factor. These findings demonstrate a potential for cellular expression of human intrinsic factor in nonparietal cells. Because such expression occurs normally at the margins of anatomical gastric regions, it suggests that local factors may influence expression of intrinsic factor.

Full text

PDF
303

Images in this article

305Fig. 1
on p.305
306Fig. 2
on p.306
307Fig. 3
on p.307
307Fig. 4
on p.307
308Fig. 5 (cont.)
on p.308
309Fig. 5
on p.309
310Fig. 6
on p.310

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aitchison M., Brown I. L. Intrinsic factor in the human fetal stomach. An immunocytochemical study. J Anat. 1988 Oct;160:211–217. [PMC free article] [PubMed] [Google Scholar]
  2. Berryman M. A., Rodewald R. D. An enhanced method for post-embedding immunocytochemical staining which preserves cell membranes. J Histochem Cytochem. 1990 Feb;38(2):159–170. doi: 10.1177/38.2.1688894. [DOI] [PubMed] [Google Scholar]
  3. Dieckgraefe B. K., Seetharam B., Alpers D. H. Developmental regulation of rat intrinsic factor mRNA. Am J Physiol. 1988 Jun;254(6 Pt 1):G913–G919. doi: 10.1152/ajpgi.1988.254.6.G913. [DOI] [PubMed] [Google Scholar]
  4. Gordon M. M., Howard T., Becich M. J., Alpers D. H. Cathepsin L mediates intracellular ileal digestion of gastric intrinsic factor. Am J Physiol. 1995 Jan;268(1 Pt 1):G33–G40. doi: 10.1152/ajpgi.1995.268.1.G33. [DOI] [PubMed] [Google Scholar]
  5. Gordon M., Chokshi H., Alpers D. H. In vitro expression and secretion of functional mammalian intrinsic factor using recombinant baculovirus. Biochim Biophys Acta. 1992 Oct 20;1132(3):276–283. doi: 10.1016/0167-4781(92)90161-r. [DOI] [PubMed] [Google Scholar]
  6. HOEDEMAEKER P. J., ABELS J., WACHTERS J. J., ARENDS A., NIEWEG H. O. INVESTIGATIONS ABOUT THE SITE OF PRODUCTION OF CASTLE'S GASTRIC INTRINSIC FACTOR. Lab Invest. 1964 Nov;13:1394–1399. [PubMed] [Google Scholar]
  7. Hoedemaeker P. J., Abels J., Wachters J. J., Arends A., Nieweg H. O. Further investigations about the site of production of Castle's gastric intrinsic factor. Lab Invest. 1966 Jul;15(7):1163–1173. [PubMed] [Google Scholar]
  8. Karam S. M., Leblond C. P. Dynamics of epithelial cells in the corpus of the mouse stomach. I. Identification of proliferative cell types and pinpointing of the stem cell. Anat Rec. 1993 Jun;236(2):259–279. doi: 10.1002/ar.1092360202. [DOI] [PubMed] [Google Scholar]
  9. Karam S. M., Leblond C. P. Dynamics of epithelial cells in the corpus of the mouse stomach. II. Outward migration of pit cells. Anat Rec. 1993 Jun;236(2):280–296. doi: 10.1002/ar.1092360203. [DOI] [PubMed] [Google Scholar]
  10. Karam S. M., Leblond C. P. Dynamics of epithelial cells in the corpus of the mouse stomach. III. Inward migration of neck cells followed by progressive transformation into zymogenic cells. Anat Rec. 1993 Jun;236(2):297–313. doi: 10.1002/ar.1092360204. [DOI] [PubMed] [Google Scholar]
  11. Kelly E. J., Lagopoulos M., Primrose J. N. Immunocytochemical localisation of parietal cells and G cells in the developing human stomach. Gut. 1993 Aug;34(8):1057–1059. doi: 10.1136/gut.34.8.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lee E. Y., Seetharam B., Alpers D. H., DeSchryver-Kecskemeti K. Immunohistochemical survey of cobalamin-binding proteins. Gastroenterology. 1989 Nov;97(5):1171–1180. doi: 10.1016/0016-5085(89)91687-9. [DOI] [PubMed] [Google Scholar]
  13. Levine J. S., Nakane P. K., Allen R. H. Human intrinsic factor secretion: immunocytochemical demonstration of membrane-associated vesicular transport in parietal cells. J Cell Biol. 1981 Sep;90(3):644–655. doi: 10.1083/jcb.90.3.644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Levine J. S., Nakane P. K., Allen R. H. Immunocytochemical localization of human intrinsic factor: the nonstimulated stomach. Gastroenterology. 1980 Sep;79(3):493–502. [PubMed] [Google Scholar]
  15. Lorenz R. G., Gordon J. I. Use of transgenic mice to study regulation of gene expression in the parietal cell lineage of gastric units. J Biol Chem. 1993 Dec 15;268(35):26559–26570. [PubMed] [Google Scholar]
  16. Maeda M., Asahara S., Nishi T., Mushiake S., Oka T., Shimada S., Chiba T., Tohyama M., Futai M. The rat intrinsic factor gene: its 5'-upstream region and chief cell-specific transcription. J Biochem. 1995 Jun;117(6):1305–1311. doi: 10.1093/oxfordjournals.jbchem.a124859. [DOI] [PubMed] [Google Scholar]
  17. Maiuri L., Raia V., Potter J., Swallow D., Ho M. W., Fiocca R., Finzi G., Cornaggia M., Capella C., Quaroni A. Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia. Gastroenterology. 1991 Feb;100(2):359–369. doi: 10.1016/0016-5085(91)90203-w. [DOI] [PubMed] [Google Scholar]
  18. Ramanujam K. S., Seetharam S., Ramasamy M., Seetharam B. Expression of cobalamin transport proteins and cobalamin transcytosis by colon adenocarcinoma cells. Am J Physiol. 1991 Mar;260(3 Pt 1):G416–G422. doi: 10.1152/ajpgi.1991.260.3.G416. [DOI] [PubMed] [Google Scholar]
  19. Schepp W., Heim H. K., Ruoff H. J. Comparison of the effect of PGE2 and somatostatin on histamine stimulated 14C-aminopyrine uptake and cyclic AMP formation in isolated rat gastric mucosal cells. Agents Actions. 1983 Apr;13(2-3):200–206. doi: 10.1007/BF01967331. [DOI] [PubMed] [Google Scholar]
  20. Schepp W., Ruoff H. J., Miederer S. E. Cellular origin and release of intrinsic factor from isolated rat gastric mucosal cells. Biochim Biophys Acta. 1983 Dec 19;763(4):426–433. doi: 10.1016/0167-4889(83)90105-2. [DOI] [PubMed] [Google Scholar]
  21. Simpson K. W., Alpers D. H., De Wille J., Swanson P., Farmer S., Sherding R. G. Cellular localization and hormonal regulation of pancreatic intrinsic factor secretion in dogs. Am J Physiol. 1993 Jul;265(1 Pt 1):G178–G188. doi: 10.1152/ajpgi.1993.265.1.G178. [DOI] [PubMed] [Google Scholar]
  22. Smolka A., Donaldson R. M., Jr Monoclonal antibodies to human intrinsic factor. Gastroenterology. 1990 Mar;98(3):607–614. doi: 10.1016/0016-5085(90)90279-a. [DOI] [PubMed] [Google Scholar]
  23. Tominaga K. Distribution of parietal cells in the antral mucosa of human stomachs. Gastroenterology. 1975 Dec;69(6):1201–1207. [PubMed] [Google Scholar]
  24. Vaillant C., Horadagoda N. U., Batt R. M. Cellular localization of intrinsic factor in pancreas and stomach of the dog. Cell Tissue Res. 1990 Apr;260(1):117–122. doi: 10.1007/BF00297496. [DOI] [PubMed] [Google Scholar]
  25. Wahlstedt V., Gräsbeck R. Cobalamin-binding proteins in human urine: identification and quantitation. J Lab Clin Med. 1985 Oct;106(4):439–446. [PubMed] [Google Scholar]

Articles from Journal of Anatomy are provided here courtesy of Anatomical Society of Great Britain and Ireland

RESOURCES