Active Synthesis of Mouse Polymeric Immunoglobulin Receptor in the Epithelial Cells of the Distal Urinary Tubule in Kidney

Asano, Masaharu; Saito, Manabu; Suguro, Hisashi; Nomura, Hajime; Inage, Toshihiko; Moro, Itaru

doi:10.1111/j.0300-9475.2004.01456.x

Cited by 9 publications

(14 citation statements)

References 26 publications

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“…In control kidneys, pIgR expression is low or absent in most tubules, except for occasional cells in D. biflorus agglutinin-negative tubules (Fig. 1C), consistent with a previous report (19).…”

Section: Pigr Is Expressed In Renal Cyst-lining Cells and Processedsupporting

confidence: 92%

“…RNA (2 g) was converted to cDNA using Moloney murine leukemia virus reverse transcriptase reverse transcriptase (Promega Corp., Madison, WI). The following primers were used for qPCR amplification: ms pIgR, 5Ј-gccaaaccttgaggtgacg-3Ј (forward) and 5Ј-taccagccttcatcttccttactgaccggg-3Ј (reverse) (19); crossspecies ␤-actin, 5Ј-gaagtgtgacgttgacatcc-3Ј (forward) and 5Ј-acagagtacttgcgctcagg-3Ј (reverse) (26). The amplification program included an annealing temperature of 55°C and used GoTaq qPCR Master Mix (Promega) and the Stratagene Mx3000P qPCR system (Agilent Technologies, Inc., Santa Clara, CA).…”

Section: Methodsmentioning

confidence: 99%

“…dIgA is typically produced by plasma cells located in the lamina propria, near the basolateral surface of mucosal epithelia. pIgR has been found in mouse and rat kidney tubule epithelial cells (19), and pIgR expression can be regulated by water deprivation, vasopressin administration, or renal ischemia-reperfusion in rats (20,21). dIgA can be found in urine, suggesting that it can reach the urinary space by pIgR-mediated transcytosis (21).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Exploitation of the Polymeric Immunoglobulin Receptor for Antibody Targeting to Renal Cyst Lumens in Polycystic Kidney Disease

Olsan

Matsushita

Rezaei

et al. 2015

Journal of Biological Chemistry

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Section: Pigr Is Expressed In Renal Cyst-lining Cells and Processedsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Exploitation of the Polymeric Immunoglobulin Receptor for Antibody Targeting to Renal Cyst Lumens in Polycystic Kidney Disease

Olsan

Matsushita

Rezaei

et al. 2015

Journal of Biological Chemistry

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“…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.…”

Section: E Coli Expressing P Fimbriae Decrease Pigr Protein Levels Isupporting

confidence: 68%

“…We and others have localized pIgR protein in the mouse kidney (32,33). We are the first to demonstrate that infection caused by P(ϩ) E. coli decreases pIgR expression in the cortical nephron segments.…”

Section: E Coli Expressing P Fimbriae Decrease Pigr Protein Levels Imentioning

confidence: 62%

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

Rice¹,

Peng²,

Spence³

et al. 2005

Journal of the American Society of Nephrology

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P fimbriae are proteinaceous appendages on the surface of Escherichia coli bacteria that mediate adherence to uroepithelial cells. E. coli that express P fimbriae account for the majority of ascending urinary tract infections in women with normal urinary tracts. The hypothesis that P fimbriae on uropathic E. coli attach to renal epithelia and may regulate the immune response to establish infection was investigated. The polymeric Ig receptor (pIgR), produced by renal epithelia, transports IgA into the urinary space. Kidney pIgR and urine IgA levels were analyzed in a mouse model of ascending pyelonephritis, using E. coli with (P؉) and without (P؊) P fimbriae, to determine whether P(؉) E. coli regulate epithelial pIgR expression and IgA transport into the urine. (P؉) E. coli establish infection and persist to a greater amount than P(؊) E. coli. P(؉)-infected mice downregulate pIgR mRNA and protein levels compared with P(؊)-infected or PBS controls at >48 h. The decrease in pIgR was associated with decreased urinary IgA levels in the P(؉)-infected group at 48 h. pIgR mRNA and protein also decline in P(؉) E. coli-infected LPS-hyporesponsive mice. These studies identify a novel virulence mechanism of E. coli that express P fimbriae. It is proposed that P fimbriae decrease pIgR expression in the kidney and consequently decrease IgA transport into the urinary space. This may explain, in part, how E. coli that bear P fimbriae exploit the immune system of human hosts to establish ascending pyelonephritis. Escherichia coli that express P fimbriae are the most common cause for upper urinary tract infections (UTI) or pyelonephritis (1). The P fimbriae mediate adherence to uroepithelial cells by binding to the Gal␣(1 to 4)Gal disaccharide on the apical surface of renal epithelial cells, glomeruli, and endothelia (2). The expression of P fimbriae on E. coli is important in establishing pyelonephritis, as P fimbriae-specific antibodies prevent the adherence of bacteria to uroepithelial cells in vitro (3) and protect animals from ascending E. coli pyelonephritis in vivo (4). Although P fimbriae are not the sole virulence factor on uropathic E. coli, pyelonephritis with P(ϩ) E. coli strains are more often associated with kidney histopathology than P(Ϫ) E. coli (5). In addition to its role as an adhesin, E. coli that express P fimbriae may determine the pattern of the local immune response via interaction with its P-specific glycosphingolipid receptors present on uroepithelial cells (6) and/or by signaling via inflammatory cytokines (7).The secretions that protect the mucosal surface of renal epithelia contain an array of host defense factors, including secretory immunoglobulins, of which IgA is the major class. 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 ...

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Production, characterization, andin vivohalf-life extension of polymeric IgA molecules in mice

Lombana¹,

Rajan²,

Zorn³

et al. 2019

mAbs

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IgA antibodies have broad potential as a novel therapeutic platform based on their superior receptor-mediated cytotoxic activity, potent neutralization of pathogens, and ability to transcytose across mucosal barriers via polymeric immunoglobulin receptor (pIgR)-mediated transport, compared to traditional IgG-based drugs. However, the transition of IgA into clinical development has been challenged by complex expression and characterization, as well as rapid serum clearance that is thought to be mediated by glycan receptor scavenging of recombinantly produced IgA monomer bearing incompletely sialylated N-linked glycans. Here, we present a comprehensive biochemical, biophysical, and structural characterization of recombinantly produced monomeric, dimeric and polymeric human IgA. We further explore two strategies to overcome the rapid serum clearance of polymeric IgA: removal of all N-linked glycosylation sites creating an aglycosylated polymeric IgA and engineering in FcRn binding with the generation of a polymeric IgG-IgA Fc fusion. While previous reports and the results presented in this study indicate that glycan-mediated clearance plays a major role for monomeric IgA, systemic clearance of polymeric IgA in mice is predominantly controlled by mechanisms other than glycan receptor clearance, such as pIgR-mediated transcytosis. The developed IgA platform now provides the potential to specifically target pIgR expressing tissues, while maintaining low systemic exposure.

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Active Synthesis of Mouse Polymeric Immunoglobulin Receptor in the Epithelial Cells of the Distal Urinary Tubule in Kidney

Cited by 9 publications

References 26 publications

Exploitation of the Polymeric Immunoglobulin Receptor for Antibody Targeting to Renal Cyst Lumens in Polycystic Kidney Disease

Exploitation of the Polymeric Immunoglobulin Receptor for Antibody Targeting to Renal Cyst Lumens in Polycystic Kidney Disease

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

Production, characterization, andin vivohalf-life extension of polymeric IgA molecules in mice

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