Skip to main content
Log in

Effects of vitamin A-deficiency and inflammation on the conducting airway epithelium of Syrian golden hamsters

  • Published:
Virchows Archiv B

Summary

The effects of vitamin A-deficiency and inflammation were studied in the conducting airways of Syrian golden hamsters. An important goal of the study was to characterize epithelial changes that occur early in vitamin A-deficiency, that might precede yet predispose to infection, and precipitate inflammatory changes in the lungs. Age-matched vitamin A-replete control and vitamin A-deprived hamsters were killed at 33 days of age (preweight-plateau); at 41 days of age (weight plateau-early weight loss); and at 48–55 days of age (prolonged weight plateau followed by weight loss). A tablet containing bromodeoxyuridine (BrdU) was implanted subcutaneously into each hamster 7 h before it was killed. No changes were seen in the conducting airway epithelium of vitamin A-deprived hamsters in the preweight plateau. However, labelling of secretory cells for BrdU was reduced 6–7 fold in the epithelium lining the lobar bronchus (p< 0.0002) and the bronchioles (p< 0.0001), and the proportions of ciliated cells were decreased (p<0.0001) at both airway levels in vitamin A-deficient hamsters in the weight plateau-early weight loss stage. Changes in cellular morphology were minimal in the intrapulmonary airway epithelium at this time but a few small focal patches of epidermoid metaplasia were seen in the tracheal epithelium. Small foci of inflammation were closely associated with the airways in the weight plateau, and the inflammation became more widespread when the deficiency was prolonged. The results suggest that the defense of the lungs to infection was impaired initially in the vitamin A-deficient hamsters by a widespread reduction in the numbers of ciliated cells throughout the epithelium of the conducting airways (trachea, bronchi, bronchioles). At the foci of inflammation, labelling of epithelial secretory cells for BrdU was greatly increased at all airway levels. A highly stratified cornifying epidermoid metaplasia developed in the tracheal epithelium, and goblet cell metaplasia developed in the cranial portion of the lobar bronchus, in association with submucosal inflammation. Goblet cell metaplasia appeared to be the only abnormality that wasnot reversed when vitamin A was restored to the diet.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Anzano MA, Lamb AJ, Olson JA (1979) Growth, appetite, sequence of pathological signs and survival following the induction of rapid, synchronous vitamin A-deficiency in the rat. J Nutr 109:1419–1431

    PubMed  CAS  Google Scholar 

  • Asmundsson T, Kilburn KH (1973) Mechanisms of respiratory tract clearance. In: Dulfano MJ (ed) Sputum. Fundamentals and clinical pathology. Ch C Thomas, Springfield, Illinois, pp107–180

    Google Scholar 

  • Beaver DL (1961) Vitamin A-deficiency in the germ-free rat. Am J Pathol 38:335–357

    PubMed  CAS  Google Scholar 

  • Bedo G, Santisteban P, Aranda A (1989) Retinoic acid regulates growth hormone gene expression. Nature 339:231–234

    Article  PubMed  CAS  Google Scholar 

  • Biesalski HK, Stofft E, Wellner U, Niederauer U, Bässler KH (1986) Vitamin A and ciliated cells. 1. Respiratory epithelia. Z Ernährungswiss 25:114–122

    Article  PubMed  CAS  Google Scholar 

  • Blackfan KD, Wolbach SB (1933) Vitamin A-deficiency in infants. J Pediatr 3:679–706

    Article  Google Scholar 

  • Bonanni F, DeLuca L (1974) Vitamin A-dependent fucose-glycopeptide from rat tracheal epithelium. Biochem Biophys Acta 343:632–637

    PubMed  CAS  Google Scholar 

  • Bonanni F, Levinson SS, Wolf G, DeLuca L (1973) Glycoproteins from the hamster respiratory tract and their response to vitamin A. Biochem Biophys Acta 297:441–451

    PubMed  CAS  Google Scholar 

  • Boren HG, Paradise LJ (1978) Cytokinetics of lung. In: Harris CC (ed) Pathogenesis and therapy of lung cancer. Marcel Dekker, New York, pp 369–418

    Google Scholar 

  • Boren HG, Pauley J, Wright EC, Kaufman DG, Smith JM, Harris CC (1974) Cell populations in the hamster tracheal epithelium in relation to vitamin A status. Int J Vit Nutr Res 44:382–390

    CAS  Google Scholar 

  • Breuer R, Christensen TG, Lucey EC, Stone PJ, Snider GL (1985) Quantitative study of secretory cell metaplasia induced by human neutrophil elastase in the large bronchi of hamsters. J Lab Clin Med 105:635–640

    PubMed  CAS  Google Scholar 

  • Breuer R, Christensen TG, Lucey EC, Stone PJ, Snider GL (1987) An ultrastructural morphometric analysis of elastase-treated hamster bronchi shows discharge followed by progressive accumulation of secretory granules. Am Rev Resp Dis 136:698–703

    PubMed  CAS  Google Scholar 

  • Bulla A, Hitze KL (1978) Acute respiratory infections: a review. WHO Bull 56:481–498

    CAS  Google Scholar 

  • Chopra DP (1982) Squamous metaplasia in organ cultures of vitamin A-deficient hamster trachea: Cytokinetic and ultrastructural alterations. J Natl Cancer Inst 69:895–905

    PubMed  CAS  Google Scholar 

  • Christensen TG, Korthy AL, Snider GL, Hayes JA (1977) Irreversible bronchial goblet cell metaplasia in hamsters with elastase-induced panacinar emphysema. J Clin Invest 59:397–404

    Article  PubMed  CAS  Google Scholar 

  • Christensen TG, Breuer R, Hornstra LJ, Lucey EC, Snider GL (1987a) The ultrastructure of hamster bronchial epithelium. Exp Lung Res 13:253–277

    Article  PubMed  CAS  Google Scholar 

  • Christensen TG, Breuer R, Hornstra LJ, Lucey EC, Stone PJ, Snider GL (1987b) An ultrastructural study of the response of hamster bronchial epithelium to human neutrophil elastase. Exp Lung Res 13:279–297

    Article  PubMed  CAS  Google Scholar 

  • Chytil F (1985) Function of vitamin A in the respiratory tract. Acta Vitaminol Enzymol [Suppl] 7:27–31

    PubMed  Google Scholar 

  • Clark JN, Marchok AC (1979) The effect of vitamin A on cellular differentiation and mucous glycoprotein synthesis in long-term rat tracheal organ cultures. Differentiation 14:175–183

    Article  PubMed  CAS  Google Scholar 

  • Dermietzel R, Yancey SB, Traub O, Willecke K, Revel J-P (1987) Major loss of the 28-kD protein of gap junction in proliferating hepatocytes. J Cell Biol 105:1925–1934

    Article  PubMed  CAS  Google Scholar 

  • Floyd EE, Jetten AM (1988) Retinoids, growth factors, and the tracheobronchial epithelium. Lab Invest 59:1–4

    PubMed  CAS  Google Scholar 

  • Ganguly J, Rao MRS, Murthy SK, Sarada K (1980) Systemic mode of action of vitamin A. In: Munson PL, Glover J, Diczfalusy E, Olson RE (eds) Vitamins and hormones. Advances in research and applications. Academic Press, New York, pp 1–54

    Google Scholar 

  • Hayes KC (1971) On the pathophysiology of vitamin A-deficiency. Nutr Rev 29:3–6

    Article  PubMed  CAS  Google Scholar 

  • Hayes JA, Christensen TG (1978) Bronchial mucus hypersecretion induced by elastase in hamsters: ultrastructural appearances. J Pathol 125:25–31

    Article  PubMed  CAS  Google Scholar 

  • Hoyt RF, Sorokin SP, Feldman H (1982) Small-granule (neuro) endocrine cells in the infracardiac lobe of a hamster lung. Number, subtypes, and distribution. Exp Lung Res 3:273–298

    Article  PubMed  Google Scholar 

  • Karnovsky MJ (1965) A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy. J Cell Biol [Abstr] 27:137A

    Google Scholar 

  • Kelly J (1990) State of the Art. Cytokines of the lung. Am Rev Resp Dis 141:765–788

    Google Scholar 

  • Lee T-C, Wu R, Brody AB, Barrett JC, Nettesheim P (1984) Growth and differentiation of hamster tracheal epithelial cells in culture. Exp Lung Res 6:27–45

    Article  PubMed  CAS  Google Scholar 

  • McDowell EM, Keenan KP, Huang M (1984a) Effects of vitamin A-deprivation on hamster tracheal epithelium. Virchows Arch [B] 45:197–219

    CAS  Google Scholar 

  • McDowell EM, Keenan KP, Huang M (1984b) Restoration of mucociliary tracheal epithelium following deprivation of vitamin A. Virchows Arch [B] 45:221–240

    CAS  Google Scholar 

  • McDowell EM, Newkirk C, Coleman B (1985) Development of hamster tracheal epithelium. II. Cell proliferation in the fetus. Anat Rec 213:448–456

    Article  PubMed  CAS  Google Scholar 

  • McDowell EM, Ben T, Coleman B, Chang S, Newkirk C, DeLuca LM (1987) Effects of retinoic acid on the growth and morphology of hamster tracheal epithelial cells in primary culture. Virchows Arch [B] 54:38–51

    CAS  Google Scholar 

  • McDowell EM, Combs JW, Newkirk C (1983) A quantitative light and electron microsopic study of hamster tracheal epithelium with special attention to so-called intermediate cells. Exp Lung Res 4:205–226

    Article  PubMed  CAS  Google Scholar 

  • McDowell EM, DeSanti AM, Strum JM (1989) Correlations between blood glucose levels and bromodeoxyuridine labelling indices of pancreatic islet cells following streptozotocin administration to pregnant Syrian golden hamsters. Virchows Arch [B] 57:223–230

    CAS  Google Scholar 

  • Mowry RW, Winkler CH (1956) Coloration of acidic carbohydrates of bacteria and fungi in tissue sections with special reference to capsules of cryptococcus neoformans, pneumococci and staphylococci. Am J Pathol 32:628–629

    Google Scholar 

  • Mullen JBM, Wright JL, Wiggs BR, Pare PD, Hogg JC (1985) Reassessment of inflammation of airways in chronic bronchitis. Br Med J 291:1235–1239

    CAS  Google Scholar 

  • Newhouse M, Sanchis J, Bienenstock J (1976) Lung defense mechanisms. New Eng J Med 295:990–998

    PubMed  CAS  Google Scholar 

  • Oberg KC, Soderquist AM, Carpenter G (1988) Accumulation of epidermal growth factor receptors in retinoic acid-treated fetal rat lung cells is due to enhanced receptor synthesis. Molec Endocrinol 2:959–965

    CAS  Google Scholar 

  • Plopper CG, Alley JL, Weir AJ (1986) Differentiation of tracheal epithelium during fetal lung maturation in the Rhesus monkeymacaca mulatta. Am J Anat 175:59–71

    Article  PubMed  CAS  Google Scholar 

  • Port CD, Baxter DW, Harris CC (1974) Surface morphology of tracheal epithelium in vitamin A-deficiency and reversal. In: Karbe E, Park JF (eds) Experimental lung cancer. Carcinogenesis and bioassays. Springer, Berlin Heidelberg New York, pp 257–264

    Google Scholar 

  • Roberts AB, Sporn MB (1984) Cellular biology and biochemistry of the retinoids. In: Sporn MB, Roberts AB, Goodman DS (eds) The retinoids, vol 2. Academic Press, New York, pp 209–285

    Google Scholar 

  • Rutten AAJJL, Wilmer JWGM, Beems RB (1988a) Effects of alltrans retinol and cigarette smoke condensate on hamster tracheal epithelium in organ culture. I. A cell proliferation study. Virchows Arch [B] 55:167–175

    CAS  Google Scholar 

  • Rutten AAJJL, Beems RB, Wilmer JWGM (1988b) Effects of all-trans retinol and cigarette smoke condensate on hamster tracheal epithelium in organ culture. II. A histomorphological study. Virchows Arch [B] 55:177–186

    CAS  Google Scholar 

  • Salley JJ, Bryson WF (1957) Vitamin A-deficiency in the hamster. J Dent Res 36:935–944

    PubMed  CAS  Google Scholar 

  • Shami SG, Martinez LA, Evans MJ (1986) The role of migrating inflammatory cells in proliferation of lung interstitium and epithelium. Chest 89:170S-173S

    Google Scholar 

  • Shapiro SS (1986) Retinoids and epithelial differentiation. In: Sherman MI (ed) Retinoids and cell differentiation. CRC Press, Boca Raton Florida, pp 29–59

    Google Scholar 

  • Shields PA, Jeffery PK (1987) The combined effects of vitamin A-deficiency and cigarette smoke on rat tracheal epithelium. Br J Exp Pathol 68:705–717

    PubMed  CAS  Google Scholar 

  • Shoji S, Rickard KA, Takizawa H, Ertl RF, Linder J, Rennard SI (1990) Lung fibroblasts produce growth stimulatory activity for bronchial epithelial cells. Am Rev Resp Dis 141:433–439

    PubMed  CAS  Google Scholar 

  • Sibille Y, Reynolds HY (1990) State of the Art. Macrophages and polymorphonuclear neutrophils in lung defense and injury. Am Rev Resp Dis 141:471–501

    PubMed  CAS  Google Scholar 

  • Sigler RE, Newkirk C, McDowell EM (1988) Histogenesis and morphogenesis of epidermoid metaplasia in hamster tracheal organ expiant culture. Virchows Arch [B] 55:47–55

    CAS  Google Scholar 

  • Snider GL, Lucey EC, Christensen TG, Stone PJ, Calore JD, Catanese A, Franzblau C (1984) Emphysema and bronchial secretory cell metaplasia induced in hamsters by human neutrophil products. Am Rev Respir Dis 129:155–160

    PubMed  CAS  Google Scholar 

  • Sorokin SP, Hoyt RF (1978) PAS-lead hematoxylin as a stain for small-granule endocrine cell populations in the lungs, other pharyngeal derivatives and the gut. Anat Rec 192:245–260

    Article  PubMed  CAS  Google Scholar 

  • Strum JM, Latham PS, Schmidt ML, McDowell EM (1985) Vitamin A deprivation in hamsters. Correlations between tracheal epithelial morphology and serum/tissue levels of vitamin A. Virchows Arch [B] 50:43–57

    Article  CAS  Google Scholar 

  • Strum JM, Ito T, Philpot RM, DeSanti AM, McDowell EM (1990a) The immunocytochemical detection of cytochrome-P450 monoxygenase in the lungs of fetal, neonatal, and adult hamsters. Am J Resp Cell Molec Biol 2:493–501

    CAS  Google Scholar 

  • Strum JM, Singh G, Katyal SL, McDowell EM (1990b) Immuno-chemical localization of Clara cell protein by light and electron microscopy in conducting airways of fetal and neonatal hamster lung. Anat Record 227:77–86

    Article  CAS  Google Scholar 

  • Sweet LK, K’Ang HJ (1935) Clinical and anatomic study of avitaminosis A among the Chinese. Am J Dis Child 50:699–734

    CAS  Google Scholar 

  • Vyas D, Chandra RK (1984) Vitamin A and immunocompetence. In: Watson RR (ed) Nutrition,disease resistance and immune function. Marcel Dekker, New York, pp 325–343

    Google Scholar 

  • WHO (1989) Control of vitamin A deficiency: the role of the expanded programme on immunization. WHO Bull 67:330–331

    Google Scholar 

  • West KP, Howard GR, Sommer A (1989) Vitamin A and infection: Public health implications. Annu Rev Nutr 9:63–86

    Article  PubMed  CAS  Google Scholar 

  • Wong Y-C, Buck RC (1971) An electron microscopic study of metaplasia of the rat tracheal epithelium in vitamin A-deficiency. Lab Invest 24:55–66

    PubMed  CAS  Google Scholar 

  • Zile MH, Cullum ME (1983) The function of vitamin A: current concepts. Proc Soc Exp Biol Med 172:139–152

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This is contribution no. 2911 from the Pathobiology Laboratory

Rights and permissions

Reprints and permissions

About this article

Cite this article

McDowell, E.M., DeSanti, A.M., Newkirk, C. et al. Effects of vitamin A-deficiency and inflammation on the conducting airway epithelium of Syrian golden hamsters. Virchows Archiv B Cell Pathol 59, 231–242 (1990). https://doi.org/10.1007/BF02899409

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02899409

Key words

Navigation