 |
||||
| 2008 JASN IMPACT FACTOR 7.505 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
|
||||
| 2008 JASN IMPACT FACTOR 7.505 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
*
Service de Néphrologie A, Assistance
Publique-Hôpitaux de Paris, Institut National
de la Santé et de la Recherche
Médicale U489 et Association Claude Bernard,
Hôpital Tenon, Paris, France.
Institut National de la Santé et de la
Recherche Médicale U277, Institut Pasteur,
Paris, France.
Correspondence to Dr. Jean-Philippe Haymann, Service de Néphrologie A, Hôpital Tenon, 4 Rue de la Chine, 75020 Paris, France. Phone: +33 1 56 01 65 10; Fax: +33 1 56 01 79 68; E-mail: jean-philippe.haymann{at}tnn.ap-hop-paris.fr
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
receptors CD16, CD32, and CD64 on GEC yielded negative results
(3,4,5,6).
Another Fc receptor, known as the neonatal Fc receptor (FcRn), has
been cloned from rodents (7)
and human subjects (8). This
receptor is an MHC class I-like membrane protein associated with
ß2-microglobulin. FcRn is considered to be involved in IgG
transport from the blood of the mother to that of the fetus during pregnancy
(8,9,10,11,12,13)
and from the milk of the mother to the neonate during lactation
(14,15,16).
The ability of this receptor to bind IgG with higher affinity at the acidic pH
encountered in the gut lumen, compared with the neutral plasma pH, is thought
to be important in the latter function
(16,17,18).
However, FcRn function is not restricted to the transfer of IgG from mother to
offspring. Indeed, FcRn, which is transcribed in many adult tissues
(7,8,19),
has been identified as the "IgG protection" receptor hypothesized
by Brambell et al.
(20) to explain the
paradoxically long half-life of IgG, relative to the half-lives of other
plasma proteins. This has led to the hypothesis that FcRn is expressed on
endothelial cells
(21,22,23).
To date, the expression of FcRn on extracellular plasma membranes has been
reported only for enterocytes and hepatocytes, whereas FcRn appears to be
localized exclusively in the cytoplasm, associated with acidified endosomes,
in syncytiotrophoblast cells and some endothelial cells
(13,23).
FcRn mRNA has been detected by Northern blot analysis of human kidneys (8), but the precise localization of this receptor on the different structures of the kidney has not been investigated. Therefore, we raised the question of whether the binding of AgIgG or Fc fragments to GEC may be linked to the presence of this receptor. We show here that this receptor is expressed on GEC in vivo and in vitro, as well as on the brush border of proximal tubular cells. These data raise interesting questions regarding the relevance of this receptor in physiologic processes and in some glomerular diseases, such as membranous nephropathy.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Cell Culture
Human GEC were isolated from normal tissue obtained from nephrectomies and
were characterized as described previously
(25). The cells were cultured
in RMPI 1640 (Life Technologies) containing 10% heat-inactivated fetal calf
serum and 2 mM L-glutamine, and they were used between passages 3 and 4. A
stable GEC cell line, E56 10A1 (hereafter referred to as E56), with a
phenotype similar to that of primary cultures of GEC and podocytes in
vivo
(25,26)
was used between passages 60 and 80. A human choriocarcinoma cell line (BEWO)
was obtained from the European Collection of Animal Cell Cultures (no.
86082803) at passage 196 and was cultured in Ham's F-12 medium (Life
Technologies) containing 2 mM glutamine and 10% fetal calf serum.
Immunofluorescence Study
Normal portions of noninvolved poles from three tumor nephrectomy specimens
were studied. The tissues were rapidly frozen in liquid nitrogen, and
2-µm-thick cryostat sections were fixed in 4% paraformaldehyde for 10 min
and washed in phosphate-buffered saline (PBS). The sections were incubated
with the rabbit antiserum to FcRn (at a dilution of 1:40) for 30 min at room
temperature, washed extensively with PBS, and incubated with FITC-anti-rabbit
IgG for 30 min. Double staining was performed using a monoclonal antibody to
CD31 (dilution 1:100; Dako, Glostrup, Denmark), an endothelial cell marker,
and a Texas red-labeled anti-mouse IgG (Vector Laboratories, Burlingame, CA)
for detection. The slides were then washed and photographs were taken using
immunofluorescence microscopy.
Immunohistochemical Study
The rabbit polyclonal anti-FcRn was detected using the
biotinavidin-peroxidase-coupled technique. In brief, the tissue sections were
blocked with 10% normal human serum before incubation with the specific rabbit
polyclonal anti-FcRn antibody (dilution 1:320) for 1 h at room temperature.
After being washed with PBS, the sections were incubated with a biotinylated
anti-rabbit antibody (Dakopatts, Glostrup, Denmark) and then incubated with
avidin coupled to peroxidase (Amersham, Buckinghamshire, United Kingdom),
which was detected with 3-amino-9-ethylcarbazole in the presence of
H2O2. Sections were then counterstained with
hematoxylin. Negative control samples were prepared using nonimmune rabbit
antiserum (dilution 1:320).
Reverse Transcription-PCR
Explanted isolated glomeruli from three different specimens were obtained
by microdissection, as described
(27). Total RNA was extracted
from microdissected glomeruli and cultured cells by ultracentrifugation on a
CsCl cushion (28). cDNA was
synthesized from 10 µg of total RNA, using 100 pmol of (dT)17
primer, 25 U of RNasin (Promega, Madison, WI), and 10 U of avian
myeloblastosis virus reverse transcriptase (Boehringer, Mannheim, Germany), in
the buffer provided. For control samples, reverse transcriptase was omitted.
cDNA was diluted with water to a final volume of 100 µl. PCR was performed
using the following mixture: 25 U/ml Goldstar Taq DNA polymerase
(Eurogentec, Seraing, Belgium) in the buffer provided, 2.5 mM
MgCl2, 0.2 mM dNTP, and 0.5 µM levels of each primer. Three
microliters of cDNA were used as the template, in a 30-µl final volume.
Forty rounds of amplification, each consisting of 30 s at 94°C, 30 s at
60°C, and 30 s at 72°C, were then performed in a 9600 GeneAmp
thermocycler (Perkin Elmer, Foster City, CA).
The following oligonucleotides (purchased from Eurogentec) were used,
yielding an expected 369-bp product from cDNA: FcRn1,
5'-CAAAGCTTTGGGGGGAAAAG-3' (hybridizing in the 
1 domain);
FcRn2, 5'-TGCAGGTAAGCACGGAAAAG-3' (hybridizing in the 3
domain). Sequencing of the PCR product was performed with the ABI Prism dye
terminator reaction kit (Perkin Elmer), using the recommended protocol; the
product was analyzed using a 373A automated DNA sequencer (Applied Biosystems,
Foster City, CA).
Immunoblot Analysis
Cell membranes from E56 cells and isolated glomeruli (obtained after
sieving) were prepared as described previously
(29). Briefly, the cells were
rapidly washed three times with cold Krebs-Henseleit buffer (118 mM NaCl, 5 mM
KCl, 1.1 mM MgSO4, 2.5 mM CaCl2, 1.2 mM
KH2PO4, 25 mM NaHCO3, pH 7.4) and scraped
into homogenization buffer (5 mM Tris-HCl, pH 7.4, containing 0.25 M sucrose,
500 U/ml Trasylol (Bayer Pharma, Puteaux, France), 1 mM ethylene
glycol-bis(ß-aminoethyl
ether)-N,N,N',N'-tetra-acetic acid, and 1 mM
phenylmethylsulfonyl fluoride). The cells were homogenized at 0°C in a
Teflon Potter homogenizer. Two milliliters of the homogenate were loaded on 1
ml of 20 mM Tris-HCl, pH 7.5, containing 1.45 M sucrose. After centrifugation
at 35,000 x g for 30 min, the membranes at the interface were
collected, pelleted at 40,000 x g for 20 min, and washed in 10
mM Hepes, pH 7.5, containing 0.2 mM CaCl2, 5 mM MgCl2,
250 U/ml Trasylol, and 0.5 mM phenylmethylsulfonyl fluoride. The cell
membranes were extracted in 5% sodium dodecyl sulfate. Protein concentrations
in the extracts were determined by the method of Peterson
(30). The extracts and
recombinant rat FcRn were resolved on 12% polyacrylamide denaturing gels and
transferred to nylon membranes. The membranes were blocked with 5% nonfat milk
in PBS and probed with rabbit antiserum to FcRn (dilution 1:500) or nonimmune
control serum (dilution 1:500) overnight at 4°C. Unbound antibodies were
removed by washing in PBS with 0.05% (vol/vol) Tween 20. A second antibody,
alkaline phosphatase-conjugated goat anti-rabbit IgG, was then applied for 30
min at 37°C, and the unbound antibody was removed by washing as described
above. Immunoreactivities were revealed with nitroblue
tetrazolium/5-bromo-4-chloro-3-indolyl phosphate substrate (Promega).
Flow Cytometric Analysis
E56 cells were detached with 5 mM ethylenediaminetetra-acetic acid, washed
three times with PBS, pH 7.4, and incubated for 30 min with either rabbit
anti-FcRn, nonimmune rabbit serum (as a negative control), anti-CD16,
anti-CD32, or anti-CD64. After washing with PBS, the cells were incubated with
FITC-conjugated goat anti-rabbit IgG or anti-mouse IgG for 1 h at room
temperature, washed, and analyzed using a flow cytometer (Beckton Dickinson,
Mountain View, CA). Data were analyzed with CellQuest software (Beckton
Dickinson). Dead cells were excluded on the basis of propidium iodide
incorporation.
Labeling of AgIgG and Binding Assays
AgIgG was labeled with Na125I, by the Iodogen method (Pierce,
Rockford, IL), to a specific activity of 0.5 Ci/µmol. Primary GEC cultures
or E56 cells were grown to confluence in 100-mm-diameter culture plates (Nunc,
Roskilde, Denmark). The cells were detached as described previously and
resuspended in binding buffer (Hanks' balanced salt solution, with 10 mM
Hepes, pH 6.0 or 8.0, containing 0.25% bovine serum albumin). The cells were
pelleted, washed, and resuspended in binding buffer at approximately
106 cells/ml. For binding assays, 3 x 105 cells in
400 µl were mixed with 125I-AgIgG (106 cpm), with or
without unlabeled AgIgG (to measure nonspecific binding). The cells were
allowed to bind AgIgG at 4°C for 24 h with gentle stirring, transferred to
Eppendorf tubes, and pelleted at 2000 rpm for 2 min at 4°C. After three
washes with Hanks' balanced salt solution, pH 6.0 or pH 8.0, cell-associated
radioactivity was counted in a gamma counter. All experiments were performed
in triplicate.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Although the immunofluorescence patterns exclude staining of mesangial cells, the presence of FcRn on podocytes or endothelial cells is an important matter of debate, because endothelial cells in liver and muscles were shown to express this receptor (23). To carefully address this question, double staining with an endothelium-specific marker (CD31) and immunohistochemical assays were performed. Figure 1C indicates the different distributions of FcRn and CD31 in glomeruli, confirming the podocyte localization of FcRn. The absence of endothelial cell staining was clearly demonstrated in the immunohistochemical analyses (Figure 1E), although very small amounts of FcRn might not have been detected.
Total microdissected glomerular RNA extracts from three different specimens were tested for the presence of FcRn mRNA. Reverse transcription (RT)-PCR was performed using primers specific for human FcRn. As shown in Figure 2, a PCR product of the expected size was obtained from all lines. Sequencing of this PCR fragment demonstrated 100% identity with the previously reported sequence of human FcRn (8). To biochemically assess the specificity of the FcRn antiserum, we performed Western blotting of isolated glomerular extracts, which revealed the presence of two bands of approximately 45 kD, consistent with two glycosylated forms of the FcRn heavy chain (Figure 3, lane 1).
|
|
Characterization of the FcRn on Immortalized GEC
To perform functional assays on this receptor, we took advantage of the
generation of an immortalized human GEC line, E56, in our laboratory
(25). Before this model could
be considered valid, however, we needed to confirm that the expression of Fc
receptors mirrored the in vivo situation. Therefore, after having
confirmed the binding of AgIgG to E56 cells in flow cytometric assays (data
not shown), we analyzed the expression of the Fc receptor candidates, namely
CD16, CD32, CD64, and FcRn.
First, we investigated the expression of CD16, CD32, CD64, and FcRn on E56
cells by flow cytometry. As shown in Figure
4, the rabbit antiserum to rat FcRn yielded modest but significant
staining of E56 cells, whereas normal rabbit serum did not. In contrast,
monoclonal antibodies to the three myeloid Fc receptors (CD16, CD32,
and CD64) did not stain E56 cells at all.
|
Total RNA was extracted from either E56 cells, primary cultured GEC, or a trophoblastic cell line chosen as a positive control (BEWO). As shown in Figure 5, a RT-PCR product of the expected size was obtained from all lines. There was no genomic DNA contamination, because PCR performed on GEC total RNA without reverse transcriptase yielded negative results. Furthermore, the two PCR primers used are expected to hybridize with two different exons. No RT-PCR product for CD16, CD32, or CD64 could be detected in GEC using specific primers (data not shown).
|
Finally, Western blotting experiments on E56 cell membrane extracts under
nonreducing conditions revealed the presence of a wide specific band of 40 to
45 kD (Figure 3, lane 3), which
may represent different glycosylated forms of the FcRn heavy chain, similar to
the recombinant rat FcRn (Figure
3, lane 5). As shown for recombinant rat FcRn, the 80-kD band
indicates an FcRn dimer form (Figure
3, lane 5). Taken together, these data demonstrate that the E56
cell line expresses the FcRn but not the other Fc receptors (CD16,
CD32, and CD64), similar to GEC expression in vivo.
A characteristic feature of the FcRn is its higher affinity for Fc at pH 6.0 to 6.5, compared with pH 7.5 to 8.0 (8,12,17,19), a property that is thought to be responsible for the trafficking of IgG from the gut lumen to the bloodstream in neonates. Using 125I-AgIgG, we investigated the pH dependence of the binding of AgIgG on E56 cells. The results showed that although 125I-AgIgG could bind to GEC in a specific manner at both pH 6 and pH 8, specific binding levels were much lower under the latter conditions (Figure 6). Similar results were obtained using primary cultured GEC (data not shown).
|
To further demonstrate the identity of the AgIgG binding site with the FcRn, we performed an inhibition assay with the polyclonal antiserum to rat FcRn. The binding of 125I-AgIgG to GEC at pH 6 was inhibited by 80% in the presence of this specific antiserum, compared with nonimmune serum (Figure 7).
|
Moreover, we performed an inhibition experiment at pH 6 using increasing concentrations of unlabeled AgIgG, which further demonstrated that the binding of 125I-AgIgG to GEC was specific and saturable. Because AgIgG is heterogeneous in size (31), it is difficult to perform Scatchard analysis of such data. Postulating a molecular mass of AgIgG of approximately 106 D, we estimated the Kd to be approximately 10-6 to 10-7 M, with 2500 binding sites/cell (data not shown).
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The absence of IgG background staining on podocytes in immunocytochemical assays, despite the presence of an Fc receptor on those cells, is explained by the low affinity of the receptor. Indeed, this low-affinity receptor (especially at pH 7.2 to 7.4) binds only multimers of IgG, in the same way that CD16 and CD32 (two other low-affinity Fc receptors) bind in vitro only IgG aggregates in solution and no IgG monomers. This finding is fully consistent with our own observations and previous reports, in which only AgIgG (1) or IgG-coated polystyrene latex particles (2) bound to podocytes ex vivo. This finding also provides an explanation for why no human IgG deposits (on podocytes) are detected in normal glomeruli in vivo; IgG must first cross the glomerular basement membrane and then at least dimerize. However, after immune complexes are immobilized in the extracellular matrix, FcRn dimerization, which enhances IgG binding affinity (32,33,34), may be facilitated.
FcRn is considered to play a key role in IgG transcytosis in many organs. In podocytes, a cellular mechanism of transcytosis has already been reported for the C5b-9 membrane attack complex (35). Because endocytosis occurs in clathrin-coated areas after incubation of AgIgG with GEC, as observed in vitro by electron microscopy (1), FcRn-mediated IgG transcytosis in GEC may be proposed. Therefore, this receptor might be involved in the clearance of immune complexes present in pathologic conditions, such as membranous nephropathy.
Another function might be attributed to this receptor in the kidney. Proteins that are filtered through the glomeruli, such as albumin, are reabsorbed primarily in renal proximal tubular cells, where they are catabolized (36). The presence of the FcRn in the brush border suggests reabsorption of IgG or Fc fragments. Indeed, it was demonstrated that infused Fc fragments were reabsorbed in renal proximal tubular cells in rats (37). However, the Fc catabolic degradation process seemed not to be located in normal kidneys, inasmuch as the serum half-life of Fc fragments was not altered by nephrectomy (38). This absence of Fc fragment degradation suggests a recycling process for IgG or Fc fragments at this location mediated by FcRn. This would agree well with the recently established role of FcRn in the protection of plasma IgG from catabolism (21,22,23). Indeed, IgG exhibits a long survival time, relative to other plasma proteins (20); however, in ß2-microglobulin knockout mice, in which the FcRn is not functional, IgG is cleared at the same accelerated rate as albumin (21). It can therefore be hypothesized that some IgG crosses the glomerular basement membrane under physiologic conditions and that FcRn on apical proximal tubular cells allows endocytosis and transport of intact IgG back to the circulation, with the kidney playing a role in this protection of IgG from catabolism. Such a hypothesis is contrary to the widely held view that the glomerular filter is an absolute barrier for IgG, a concept that is supported by the absence of detectable IgG in the ultrafiltrate (37). However, given the large volume of plasma filtered through the kidneys, even a minute leakage of IgG through the barrier might result in significant daily loss from the total IgG pool if those molecules were not recycled, with IgG remaining undetectable in the ultrafiltrate by conventional methods. A testable prediction of this hypothesis would be that in ß2-microglobulin knockout mice, the kidney would be an important site for IgG catabolism. Additional work is required to determine whether this receptor has functional relevance under physiologic conditions and/or in some human glomerulone-phritides, in which subepithelial IgG deposits are found in the glomeruli and IgG is observed in the urine.
|
Acknowledgments |
|---|
This work was supported by the Delegation de la Recherche Clinique Assistance Publique-Hôpitaux de Paris (Grant CRC97187). Dr. Levraud is the recipient of a fellowship from the Pasteur Institute. We are very grateful to Dr. Pamela Bjorkman for precious reagents. We thank Drs. Marie-Claire Gubler, Gabriel Gachelin, Pierre Verroust, Jean Kanellopoulos, and Philippe Kourilsky for helpful comments and critical reading. We thank Madeleine Delauche, Francoise Delarue, and Latifa Bouzhir for expert technical assistance.
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
receptor and IgG in human placenta term syncytiotrophoblasts.
Eur J Immunol 26:1668
-1671, 1996[Medline]
2IV collagen mRNA expression by competitive
polymerase chain reaction. J Exp Med176
: 1571-1576,1992
resolution of the
MHC-related neonatal Fc receptor. Nature372
: 336-343,1994[Medline]
This article has been cited by other articles:
 |
|
 |
|
  M. Sarav, Y. Wang, B. K. Hack, A. Chang, M. Jensen, L. Bao, and R. J. Quigg Renal FcRn Reclaims Albumin but Facilitates Elimination of IgG J. Am. Soc. Nephrol., September 1, 2009; 20(9): 1941 - 1952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Montoyo, C. Vaccaro, M. Hafner, R. J. Ober, W. Mueller, and E. S. Ward Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in mice PNAS, February 24, 2009; 106(8): 2788 - 2793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Goebl, C. M. Babbey, A. Datta-Mannan, D. R. Witcher, V. J. Wroblewski, and K. W. Dunn Neonatal Fc Receptor Mediates Internalization of Fc in Transfected Human Endothelial Cells Mol. Biol. Cell, December 1, 2008; 19(12): 5490 - 5505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-W. Qiao, K. Kobayashi, F.-E. Johansen, L. M. Sollid, J. T. Andersen, E. Milford, D. C. Roopenian, W. I. Lencer, and R. S. Blumberg Dependence of antibody-mediated presentation of antigen on FcRn PNAS, July 8, 2008; 105(27): 9337 - 9342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Akilesh, T. B. Huber, H. Wu, G. Wang, B. Hartleben, J. B. Kopp, J. H. Miner, D. C. Roopenian, E. R. Unanue, and A. S. Shaw From the Cover: Podocytes use FcRn to clear IgG from the glomerular basement membrane PNAS, January 22, 2008; 105(3): 967 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Akilesh, G. J. Christianson, D. C. Roopenian, and A. S. Shaw Neonatal FcR Expression in Bone Marrow-Derived Cells Functions to Protect Serum IgG from Catabolism J. Immunol., October 1, 2007; 179(7): 4580 - 4588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Vaccaro, R. Bawdon, S. Wanjie, R. J. Ober, and E. S. Ward Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies PNAS, December 5, 2006; 103(49): 18709 - 18714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Abbate, C. Zoja, and G. Remuzzi How Does Proteinuria Cause Progressive Renal Damage? J. Am. Soc. Nephrol., November 1, 2006; 17(11): 2974 - 2984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. F. Dall'Acqua, P. A. Kiener, and H. Wu Properties of Human IgG1s Engineered for Enhanced Binding to the Neonatal Fc Receptor (FcRn) J. Biol. Chem., August 18, 2006; 281(33): 23514 - 23524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Kacskovics, Z. Kis, B. Mayer, A. P. West Jr, N. E. Tiangco, M. Tilahun, L. Cervenak, P. J. Bjorkman, R. A. Goldsby, O. Szenci, et al. FcRn mediates elongated serum half-life of human IgG in cattle Int. Immunol., April 1, 2006; 18(4): 525 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Maidji, S. McDonagh, O. Genbacev, T. Tabata, and L. Pereira Maternal Antibodies Enhance or Prevent Cytomegalovirus Infection in the Placenta by Neonatal Fc Receptor-Mediated Transcytosis Am. J. Pathol., April 1, 2006; 168(4): 1210 - 1226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Newton, Z. Wu, and N. E. Simister Characterization of basolateral-targeting signals in the neonatal Fc receptor J. Cell Sci., June 1, 2005; 118(11): 2461 - 2469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. B. Wernick, V. Haucke, and N. E. Simister Recognition of the Tryptophan-based Endocytosis Signal in the Neonatal Fc Receptor by the {micro} Subunit of Adaptor Protein-2 J. Biol. Chem., February 25, 2005; 280(8): 7309 - 7316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-J. Kim, T. E. Fandy, V. H. L. Lee, D. K. Ann, Z. Borok, and E. D. Crandall Net absorption of IgG via FcRn-mediated transcytosis across rat alveolar epithelial cell monolayers Am J Physiol Lung Cell Mol Physiol, September 1, 2004; 287(3): L616 - L622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Bitonti, J. A. Dumont, S. C. Low, R. T. Peters, K. E. Kropp, V. J. Palombella, J. M. Stattel, Y. Lu, C. A. Tan, J. J. Song, et al. Pulmonary delivery of an erythropoietin Fc fusion protein in non-human primates through an immunoglobulin transport pathway PNAS, June 29, 2004; 101(26): 9763 - 9768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Ober, C. Martinez, C. Vaccaro, J. Zhou, and E. S. Ward Visualizing the Site and Dynamics of IgG Salvage by the MHC Class I-Related Receptor, FcRn J. Immunol., February 15, 2004; 172(4): 2021 - 2029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Maillard, J.-P. Lavergne, S. Siberil, G. Faure, F. Roohvand, S. Petres, J. L. Teillaud, and A. Budkowska Fc{gamma} Receptor-like Activity of Hepatitis C Virus Core Protein J. Biol. Chem., January 23, 2004; 279(4): 2430 - 2437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Morigi, D. Macconi, C. Zoja, R. Donadelli, S. Buelli, C. Zanchi, M. Ghilardi, and G. Remuzzi Protein Overload-Induced NF-{kappa}B Activation in Proximal Tubular Cells Requires H2O2 through a PKC-Dependent Pathway J. Am. Soc. Nephrol., May 1, 2002; 13(5): 1179 - 1189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Doublier, V. Ruotsalainen, G. Salvidio, E. Lupia, L. Biancone, P. G. Conaldi, P. Reponen, K. Tryggvason, and G. Camussi Nephrin Redistribution on Podocytes Is a Potential Mechanism for Proteinuria in Patients with Primary Acquired Nephrotic Syndrome Am. J. Pathol., May 1, 2001; 158(5): 1723 - 1731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhu, G. Meng, B. L. Dickinson, X. Li, E. Mizoguchi, L. Miao, Y. Wang, C. Robert, B. Wu, P. D. Smith, et al. MHC Class I-Related Neonatal Fc Receptor for IgG Is Functionally Expressed in Monocytes, Intestinal Macrophages, and Dendritic Cells J. Immunol., March 1, 2001; 166(5): 3266 - 3276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kobayashi, Y. Suzuki, T. Tsuge, K. Okumura, C. Ra, and Y. Tomino FcRn-mediated transcytosis of immunoglobulin G in human renal proximal tubular epithelial cells Am J Physiol Renal Physiol, February 1, 2002; 282(2): F358 - F365. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
HOME
CURRENT ISSUE
ARCHIVES
JASN Express
ONLINE SUBMISSION
AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP |
