Do Heterologous Proteins Pass from Mother to Fetus in Cow, Cat and Guinea Pig?

Kulangara, Abraham C.; Schechtman, A. M.

doi:10.3181/00379727-112-27998

Cited by 5 publications

(3 citation statements)

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“…The relative degradation of both these proteins was greater than homologous IgG and no evidence of transport was found, although relatively large amounts appeared to be lost to the incubation medium by surface desorption. This pattern is not inconsistent with the limited data from experiments in vivo which suggest that, at best, only small amounts of bovine IgG and bovine serum albumin reach the fetal circulation after injection into pregnant guinea pigs (Al-Nadji, 1965;Kulangara & Schechtman, 1963).…”

Section: Degradation and Release Studiessupporting

confidence: 52%

Endocytosis and subsequent processing of 125I-labelled immunoglobulin G by guinea pig yolk sac in vitro

Douglas¹,

King²

1985

Biochemical Journal

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We have developed conditions for studying the binding, uptake, degradation and transport of 125I-labelled IgG by yolk sac in vitro. Specific binding to tissue at 4 degrees C and to paraformaldehyde-treated tissue at 37 degrees C was time- and temperature-dependent and showed saturation kinetics (Kd,4 degrees C = 2.9 X 10(-6) M, Kd,37 degrees C = 5.3 X 10(-6) M). Uptake was studied at 37 degrees C using untreated tissue (K uptake = 13.3 X 10(-6) M) and was inhibited by preincubation with metabolic poisons but not with cycloheximide. Tissue that had been incubated with 125I-labelled IgG at 37 degrees C released radiolabelled degradation products and intact 125I-labelled IgG into the medium. Experiments with paraformaldehyde-treated and untreated tissue showed that release of intact 125I-labelled IgG was mostly the result of ligand dissociation from surface binding sites. However, more 125I-labelled IgG was released from untreated tissue than could be accounted for solely by loss of surface-bound ligand and the difference was presumed to reflect uptake, transport and exocytosis of 125I-labelled IgG. Degradation of 125I-labelled IgG was inhibited by leupeptin and lysosomotropic amines. These drugs had no detectable effect on 125I-labelled IgG release. The results suggest that degradation and transport of IgG are not intimately related and are consistent with a previously proposed model for IgG transport via coated vesicles which do not fuse with lysosomes and for non-selective uptake into another class of vesicle which does fuse with lysosomes.

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Section: Degradation and Release Studiessupporting

confidence: 52%

Endocytosis and subsequent processing of 125I-labelled immunoglobulin G by guinea pig yolk sac in vitro

Douglas¹,

King²

1985

Biochemical Journal

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“…We and others have shown that the pregnant guinea pig is a good model for studying antibody transfer during pregnancy [ 17 – 21 ] and can transfer all human IgG subclasses at the end of gestation [ 18 ]. Based on these findings, we set out to test the hypothesis that, like in humans, fetal concentration of the human IgG in the pregnant guinea pig increases with gestation.…”

Section: Introductionmentioning

confidence: 99%

Gestation age dependent transfer of human immunoglobulins across placenta in timed-pregnant guinea pigs

Norton

et al. 2015

Placenta

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IntroductionWhen administered during pregnancy, antibodies and other biologic drugs that contain the Fc part of the IgG molecule can traverse the placenta. Although it is generally accepted that the FcRn receptor mediates this process, gaps remain in our understanding of underlying details in humans and in common laboratory animal species.MethodsWe expanded our previous studies in timed-pregnant guinea pigs to both measure the transport of human (h) IgG at earlier gestation ages in vivo and evaluate FcRn function in vitro using Surface Plasmon Resonance (SPR) and Madin–Darby canine kidney cells (MDCK) that express guinea pig (gp) FcRn.ResultsIn timed-pregnant guinea pigs both the average concentration of hIgG in the fetus and its ratio to maternal hIgG concentration increase exponentially with gestation age. Thus, hIgG fetal:maternal concentration ratios increase from an average of 1% to 3%, 17%, and 76% on GD ~26, 35, 46, and 54, respectively. In vitro, gpFcRn immobilized on a solid surface can bind hIgG and gpIgG preparations in a similar manner. All engineered human Fc isotype-specific constructs were internalized by MDCK-gpFcRn cells at significant levels. While not significant, their recycling and hIgG transcytosis by this cell line also trend higher than background controls.DiscussionPregnant guinea pigs exhibit similarities with humans in the degree and timing of trans-placental transfer as well as the ability of their FcRn to bind and internalize hIgG in vitro. Further studies are needed to guide building appropriate systems for the evaluation of FcRn mediated function of human immunoglobulin therapies.

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“…The guinea pig has been used for transplacental transfer studies of nutrients such as amino acids and glucose [ 24 , 25 ]. It has even been shown that homologous and heterologous guinea pig antibodies [ 26 , 27 ] as well as a commercial humanized IgG4 antibody [ 16 ] do transfer from pregnant sows to their fetuses. Most importantly, the transfer of antibodies from mother to the embryo occurs during the last third of pregnancy [ 28 ], in striking resemblance to humans, especially when compared to the different pattern observed in other rodents such as rats [ 29 ] and likely in mice, where the transfer is primarily via the GI tract and after delivery.…”

Section: Resultsmentioning

confidence: 99%

Human Antibodies Can Cross Guinea Pig Placenta and Bind Its Neonatal Fc Receptor: Implications for Studying Immune Prophylaxis and Therapy during Pregnancy

Struble¹,

Ma²,

Zhong³

et al. 2012

Clinical and Developmental Immunology

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Despite increased use of monoclonal and polyclonal antibody therapies, including during pregnancy, there is little data on appropriate animal models that could humanely be used to understand determinants of protection and to evaluate safety of these biologics in the mother and the developing fetus. Here, we demonstrate that pregnant guinea pigs can transport human IgG transplacentally at the end of pregnancy. We also observe that human IgG binds to an engineered soluble variant of the guinea pig neonatal Fc receptor in vitro in a manner similar to that demonstrated for the human variant, suggesting that this transplacental transport mirrors the receptor-based mechanism seen in humans. Using an intravenous antihepatitis B-specific immune globulin preparation as an example, we show that this transport results in neutralizing activity in the mother and the newborn that would potentially be prophylactic against hepatitis B viral infection. These preliminary data lay the groundwork for introducing pregnant guinea pigs as an appropriate model for the evaluation of antibody therapies and advancing the health of women and neonates.

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Do Heterologous Proteins Pass from Mother to Fetus in Cow, Cat and Guinea Pig?

Cited by 5 publications

References 0 publications

Endocytosis and subsequent processing of 125I-labelled immunoglobulin G by guinea pig yolk sac in vitro

Endocytosis and subsequent processing of 125I-labelled immunoglobulin G by guinea pig yolk sac in vitro

Gestation age dependent transfer of human immunoglobulins across placenta in timed-pregnant guinea pigs

Human Antibodies Can Cross Guinea Pig Placenta and Bind Its Neonatal Fc Receptor: Implications for Studying Immune Prophylaxis and Therapy during Pregnancy

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