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

Abstract

The respiratory tract in humans represents a large mucosal area exposed to the environment. The secretory immune system is the first, noninflammatory line of defence, protecting the respiratory tract from viral and bacterial infections. Secretory immunoglobulin A (S-IgA) is the major immunoglobulin present in human airway secretions [1]. The humoral secretory immune response depends on interactions between the B-cell system for the production of J-chain-containing polymeric IgA (pIgA) and the mucosal epithelium for the epithelial expression of secretory component (SC), respectively. SC is the soluble extracellular domain of the polymeric Ig receptor (pIgR) present on the basolateral surface of most epithelial cells. The pIgA antibodies produced by plasma cells are transported into mucosal secretions by transcytosis through epithelial cells [2,3]. The pIgR at the basolateral pole of the epithelium, with or without bound pIgA, is constitutively endocytosed and transported by vesicles to the apical pole, where pIgR vesicles fuse with the apical membrane. A proteolytic cleavage then occurs between the extracellular and membrane domains of the pIgR, resulting in the release of SC or S-IgA, a complex of mostly dimeric IgA (dIgA), J-chain and SC [4,5]. Immunohistology and immunofluorescence studies have demonstrated the presence of SC in bronchial epithelial cells and of IgA-containing plasma cells in the bronchial mucosa [6]. Moreover, pIgA and SC transcytosis have also been demonstrated by immunoelectron microscopy of bronchial mucosa [7]. In human pathology, decreased SC levels have been described in the bronchoalveolar lavage (BAL) fluid of asthmatic patients compared with normal controls [8]. Furthermore, a prospective study in children suggested a relationship between transient salivary IgA deficiency during the first year of life and the later development of bronchial hyperreactivity [9].The production of SC by cultured human tracheal epithelial cells has been demonstrated to be influenced by cell polarization [10]. 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. These processes were apically polarized and upregulated by interferon-γ. Among the cell lines studied, only CALU-3 expressed secretory component-messenger ribonucleic acid and produced detectable secretory component.

IL-8 Released Constitutively by Primary Bronchial Epithelial Cells in Culture Forms an Inactive Complex with Secretory Component

“…We suggest the difference lay in their use of cell lines or culture conditions in which SC is expressed at low levels. For example, the A549 cell line used by Smart and Casale (36) expresses SC at levels three orders of magnitude less than primary epithelial cells (25). Second, the culture of primary bronchial epithelial cells on uncoated plastic, for example by Abdelaziz et al (37), reduces SC expression by 30-fold compared with growth on collagen-coated plastic as shown by Fiedler et al (28).…”

“…In cultures of primary human bronchial epithelial cells isolated from enzymatic digests of segments of bronchial tubes from patients with a history of smoking and mild chronic obstructive pulmonary disease undergoing lobectomy for lung cancer, Godding et al (25) reported 15 times lower SC release. Because decreased Clara cell protein (CC10) levels have been measured in epithelial cells from smokers (26), it is possible that synthesis of other proteins such as SC may be similarly altered.…”

Airway Epithelial Cells Regulate the Functional Phenotype of Locally Differentiating Dendritic Cells: Implications for the Pathogenesis of Infectious and Allergic Airway Disease

“…Ϫ include ICAM-1 expression (27), specific lectin-binding activity (28), and the absence of secretory component (29). As such they appear to be an acceptable surrogate for the basal AECs that are in direct contact with intraepithelial DCs in vivo.…”

Lung mucosal immunity: immunoglobulin-A revisited

“…The epithelial expression of pIgR appears thus upregulated in vitro by different cytokines, especially by IFN-c both on intestinal epithelial cell lines [42] and the bronchial epithelial cell line Calu-3 [43], as well as on primary bronchial epithelial cells [44], by interacting with specific receptors expressed restrictively on the basolateral pole of these cells. Synergistically with IFN-c, IL-4 upregulates SC expression on HT-29 colon carcinoma cells [42] and Calu-3 cells [45], while the effects of these cytokines appeared additive on IgA transport.…”