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Nutrition and Disease

Zinc Deficiency Induces Membrane Barrier Damage and Increases Neutrophil Transmigration in Caco-2 Cells^1,2

³ Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione, 00178 Rome, Italy and ⁴ Dipartimento Biologia di Base ed Applicata, Università de L'Aquila, 67100 Italy

Zinc may contribute to the host defense by maintaining the membrane barrier. In this study, we questioned whether zinc deficiency affects the membrane function and junctional structure of intestinal epithelial cells, causing increased neutrophil migration. We used the Caco-2 cell line grown in control (C), zinc-deficient, or zinc-replete medium until differentiation. Zinc deprivation induced a decrease of transepithelial electrical resistance and alterations to tight and adherens junctions, with delocalization of zonula occludens (ZO-1), occludin, β-catenin, and E-cadherin. Disorganization of F-actin and β-tubulin was also found in zinc deficiency. These changes were associated with a loss of the amounts of ZO-1, occluding, and β-tubulin. In addition, zinc deficiency caused a dephosphorylation of occludin and hyperphosphorylation of β-catenin and ZO-1. Disruption of membrane barrier integrity led to increased migration of neutrophils. In addition, zinc deficiency induced an increase in the secretion of interleukin-8, epithelial neutrophil activating peptide-78, and growth-regulated oncogene-, alterations that were not found when culture medium was replete with zinc. These results provide new information on the critical role played by dietary zinc in the maintenance of membrane barrier integrity and in controlling inflammatory cell infiltration.

^* To whom correspondence should be addressed. E-mail: mengheri{at}inran.it.

Manuscript received 21 March 2008. Initial review completed 18 June 2008. Revision accepted 2 July 2008.