Regulation of the polymeric immunoglobulin receptor by water intake and vasopressin in the rat kidney

Abstract

The polymeric immunoglobulin receptor (pIgR) transports polymeric immunoglobulins (IgA) from the basolateral to the apical surface of epithelial cells. At the apical surface, its amino-terminal domain, termed secretory component (SC), is proteolytically cleaved and released either unbound (free SC) or bound to IgA. We examined the effects of changes in water balance and vasopressin on the production and secretion of the pIgR in the rat kidney in vivo. Water deprivation induced a 2.7-fold increase in the pIgR mRNA and a 2.2-fold increase in intracellular pIgR protein compared with water-loaded animals. Physiological doses of desmopressin reproduced the effects of water deprivation on mRNA and intracellular protein levels, suggesting that pIgR expression may be regulated by a vasopressin-coupled mechanism. Secretion of free SC and secretory IgA in the urine, however, correlated directly with water intake and urine flow. These results suggest that hydration status and vasopressin may affect the mucosal immunity of the kidney by regulating at different steps the epithelial cell production and secretion of the polymeric immunoglobulin transporter/secretory component.

Pyelonephritic Escherichia coli Expressing P Fimbriae Decrease Immune Response of the Mouse Kidney

“…We are the first to demonstrate that infection caused by P(ϩ) E. coli decreases pIgR expression in the cortical nephron segments. The distribution of pIgR protein seems to be similar to that of the normal rat kidney, in which we have demonstrated that pIgR protein is preferentially expressed near the luminal surface of the thick ascending limb and throughout some proximal tubules (11). The decreased pIgR staining in the cortical tubules of the P(ϩ) E. coli-infected mice suggests that pIgR protein is depleted from the apical storage vesicles of the renal epithelia, where it has been shown clearly to be stored by electron microscopy in normal mice (33), and is consistent with our findings of decreased pIgR protein levels by Western blot in the P(ϩ) E. coli-infected group at 48 h. Hence, the depletion of pIgR protein in the kidney cortex of pyelonephritis animals at 48 h (Figure 4) results from the combined effects of decreased pIgR RNA levels ( Figure 2) and the continued excretion of SC (cleaved fragment of pIgR) either attached to IgA ( Figure 5) or as FSC.…”

“…Northern blot of total RNA was performed using a formaldehyde 1% agarose gel and transferred to a nylon membrane (Schleicher & Schuell, Keene, NH) as described (11). We used the 2.2-kb SacI fragment of the full-length cDNA probe for mouse pIgR mRNA provided by Charlotte Kaetzel (25) for Northern hybridization analysis of pIgR.…”

“…IgA concentrations in urine and kidney homogenates were quantified in a sandwich ELISA modified from methods previously described (11). Briefly, 96-well polystyrene microtiter plates (Dynatech Laboratories, Chantilly, VA) were coated with 3 g/ml goat anti-mouse IgA in borate-buffered saline, samples were added in duplicate using serial dilutions and detected using polyclonal goat anti-mouse IgA-HRP and monoclonal IgA as a standard as described (27).…”

“…The polymeric Ig receptor (pIgR) is responsible for transporting these secretory immunoglobulins (S-Ig) in vesicles from the basolateral to the apical surface of epithelial cells (8 -10), including renal tubule cells. The extracellular portion of the pIgR, termed secretory component (SC), is cleaved at the apical surface and excreted into the urinary space either bound to IgA as secretory IgA (S-IgA) or unbound (free SC) (11). Our goal was to determine whether P fimbriae on E. coli affect the expression of the pIgR and the transport of IgA into the urine during ascending pyelonephritis and to determine whether pIgR expression was affected by the innate immune response to LPS in vivo.…”

Immunoglobulin Transport and Immunoglobulin Receptors

“…However, significant levels of SC were seen in tubular epithelial cells, but not glomeruli, from 51 patients with various forms of renal damage (Dobrin et al, 1975), and levels of urinary SIgA and free SC were found to be elevated in acute pyelonephritis (Svanborg Edén et al, 1985;Greenwell et al, 1995). In subsequent studies using more sensitive methods, pIgR mRNA and protein were detected in normal rat kidney, and levels were elevated after water deprivation, treatment with vasopressin, or ischemia (Rice et al, 1998(Rice et al, , 1999. Taken together, these data suggest that pIgR is normally expressed at low levels in the kidney but may be elevated in renal disease.…”