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.
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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
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
Beaver DL (1961) Vitamin A-deficiency in the germ-free rat. Am J Pathol 38:335–357
Bedo G, Santisteban P, Aranda A (1989) Retinoic acid regulates growth hormone gene expression. Nature 339:231–234
Biesalski HK, Stofft E, Wellner U, Niederauer U, Bässler KH (1986) Vitamin A and ciliated cells. 1. Respiratory epithelia. Z Ernährungswiss 25:114–122
Blackfan KD, Wolbach SB (1933) Vitamin A-deficiency in infants. J Pediatr 3:679–706
Bonanni F, DeLuca L (1974) Vitamin A-dependent fucose-glycopeptide from rat tracheal epithelium. Biochem Biophys Acta 343:632–637
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
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
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
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
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
Bulla A, Hitze KL (1978) Acute respiratory infections: a review. WHO Bull 56:481–498
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
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
Christensen TG, Breuer R, Hornstra LJ, Lucey EC, Snider GL (1987a) The ultrastructure of hamster bronchial epithelium. Exp Lung Res 13:253–277
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
Chytil F (1985) Function of vitamin A in the respiratory tract. Acta Vitaminol Enzymol [Suppl] 7:27–31
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
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
Floyd EE, Jetten AM (1988) Retinoids, growth factors, and the tracheobronchial epithelium. Lab Invest 59:1–4
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
Hayes KC (1971) On the pathophysiology of vitamin A-deficiency. Nutr Rev 29:3–6
Hayes JA, Christensen TG (1978) Bronchial mucus hypersecretion induced by elastase in hamsters: ultrastructural appearances. J Pathol 125:25–31
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
Karnovsky MJ (1965) A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy. J Cell Biol [Abstr] 27:137A
Kelly J (1990) State of the Art. Cytokines of the lung. Am Rev Resp Dis 141:765–788
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
McDowell EM, Keenan KP, Huang M (1984a) Effects of vitamin A-deprivation on hamster tracheal epithelium. Virchows Arch [B] 45:197–219
McDowell EM, Keenan KP, Huang M (1984b) Restoration of mucociliary tracheal epithelium following deprivation of vitamin A. Virchows Arch [B] 45:221–240
McDowell EM, Newkirk C, Coleman B (1985) Development of hamster tracheal epithelium. II. Cell proliferation in the fetus. Anat Rec 213:448–456
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
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
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
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
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
Newhouse M, Sanchis J, Bienenstock J (1976) Lung defense mechanisms. New Eng J Med 295:990–998
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
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
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
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
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
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
Salley JJ, Bryson WF (1957) Vitamin A-deficiency in the hamster. J Dent Res 36:935–944
Shami SG, Martinez LA, Evans MJ (1986) The role of migrating inflammatory cells in proliferation of lung interstitium and epithelium. Chest 89:170S-173S
Shapiro SS (1986) Retinoids and epithelial differentiation. In: Sherman MI (ed) Retinoids and cell differentiation. CRC Press, Boca Raton Florida, pp 29–59
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
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
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
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
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
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
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
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
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
Sweet LK, K’Ang HJ (1935) Clinical and anatomic study of avitaminosis A among the Chinese. Am J Dis Child 50:699–734
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
WHO (1989) Control of vitamin A deficiency: the role of the expanded programme on immunization. WHO Bull 67:330–331
West KP, Howard GR, Sommer A (1989) Vitamin A and infection: Public health implications. Annu Rev Nutr 9:63–86
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
Zile MH, Cullum ME (1983) The function of vitamin A: current concepts. Proc Soc Exp Biol Med 172:139–152
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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
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DOI: https://doi.org/10.1007/BF02899409