Cell polarity regulates the release of secretory component, the epithelial receptor for polymeric immunoglobulins, from the surface of HT‐29 colon carcinoma cells

Abstract

The HT-29 human colon carcinoma cell line differentiates in glucose-free medium to an enterocytic phenotype. We previously isolated a series of HT-29 subclones selected for high levels of expression of secretory component (SC), the epithelial receptor for polymeric immunoglobulins. To develop a model system for studying effects of cell polarity on SC expression and release from the cell surface, the HT-29.74 subclone was induced to differentiate in glucose-free medium. Expression of SC was induced by glucose deprivation in both the parental HT-29 cell line and, to an even greater extent, in the HT-29.74 subclone. Prolonged glucose deprivation of HT-29.74 cells resulted in morphological changes consistent with enterocytic differentiation. Metabolic radiolabeling of SC in differentiated HT-29.74 cells indicated that proteolytic cleavage of membrane-bound to free SC occurred both on the cell surface and intracellularly, possibly in a vacuolar apical compartment or intrapeithelial lumen. To study effects of cell polarity on SC release, differentiated HT-29.74 cells were depolarized by culturing in low calcium medium. Within 2 hours after transfer of the cells into low calcium medium, a burst of SC release was observed concomitant with cell depolarization. Subsequently, release of SC declined significantly and remained low as long as cells were maintained in a depolarized state. The extent of cell depolarization could be controlled by varying the extracellular calcium concentration or by substituting the divalent cation Sr++, which partially prevents depolarization, for Ca++. In either case, the magnitude of the initial burst and subsequent decline in release of SC was proportional to the extent of cell depolarization. We conclude that cell polarity plays an important role in controlling the release of SC in intestinal epithelial cells, most likely by regulating the distribution of membrane-bound SC and SC protease, which are on the basolateral and apical cell surfaces, respectively, in differentiated cells.

Free secretory component and lactoferrin of human milk inhibit the adhesion of enterotoxigenic Escherichia coli

“…Indeed, it has been shown that fucosylated oligosaccharides are associated with the inhibition of CFA 1 -and CFA2-mediated adhesion of ETEC strains26 and inhibit localised adhesion of EPEC strain^.^ Human milk contains many glycocompounds, some of which are rich in fucosylated oligosaccharides, such as Lf and free secretory component (fSC), which are found in abundance.l2' l6, 28-30 Th e secretory component (SC) mediates the transport of sIgA into external fluids on mucosal epithelial cells, and can be found in secretions both complexed with sIgA (bound SC) or as an uncomplexed 80-kDa glycoprotein called free SC. [31][32][33] This study investigated a possible role for glycoproteins from human milk in the inhibition of the adhesion (haemagglutination) induced by ETEC CFA1+ strains, assaying, step by step, every fraction obtained in the chromatographic fractionation of the milk.…”

Secretory component production by human bronchial epithelial cells is upregulated by interferon gamma

“…Previous studies have stressed the influence of epithelial cell polarization on SC secretion [10,11]. CHINTALA-CHARUVU et al [11] extensively demonstrated that depolarization, induced by calcium deprivation, significantly decreased the total release of SC by HT-29.74 human colon carcinoma cells.…”

“…CHINTALA-CHARUVU et al [11] extensively demonstrated that depolarization, induced by calcium deprivation, significantly decreased the total release of SC by HT-29.74 human colon carcinoma cells. Like FIEDLER et al [10] we found that SC release by HBEC in primary culture on permeable filters was apically polarized.…”

“…The influence of cell polarization on SC production was further stressed by studies using neoplastic colonic cells, demonstrating an enhancing effect of polarization on their in vitro SC production [11]. It is concluded that human bronchial epithelial cells produce secretory component and transcytose dimeric immunoglobulin A in vitro.…”

“…The influence of cell polarization on SC production was further stressed by studies using neoplastic colonic cells, demonstrating an enhancing effect of polarization on their in vitro SC production [11]. Cytokines such as interferon (IFN)-γ [12,13], interleukin (IL)-4 [13,14], tumour necrosis factor-α (TNF-α) [15], transforming growth factor-β (TGF-β) [16], and IL-1α and IL-1β [17] have been shown to increase SC production by intestinal epithelial cell lines.…”