Monoclonal antibodies to mammalian heat shock proteins impair mouse embryo development in vitro

Neuer, A.; Mele, Carol Ann; Liu, H C; Rosenwaks, Zev; Witkin, Steven S.

doi:10.1093/humrep/13.4.987

Cited by 69 publications

(42 citation statements)

References 22 publications

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“…HSP70 is crucial for the maintenance of cellular homeostasis during normal cell growth and for survival during and after various cellular stresses (25). In 1998, Neuer et al (26) indicated that mouse embryonic growth was markedly inhibited when monoclonal anti-HSP70 antibodies were supplemented to mouse embryos at the 2-cell stage, thus proving that HSP70 plays important roles in protecting normal embryonic development.…”

Section: Discussionmentioning

confidence: 99%

Effects of diagnostic ultrasound on HSP70 expression in chorionic villi in rats during early pregnancy and the role of HSP70 in apoptosis in chorionic villi

Liu

Hou

Liang

et al. 2013

International Journal of Molecular Medicine

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Abstract. The aim of this study was to investigate the effects of diagnostic ultrasound on chorionic villi during early pregnancy in rats through the examination of heat shock protein 70 (HSP70) expression and apoptosis in chorionic villi. Using TUNEL, RT-PCR, western blot analysis and immunohistochemistry, the extent of apoptosis and the gene/ protein expression of HSP70, Bcl-2 and Bax was determined in the samples of the chorionic villus from the rats during early pregnancy. Compared with the unexposed group, there were clear signs that apoptosis had occurred in the villi exposed to ultrasound for 30 min. The expression of HSP70 and Bax in the villi gradually increased with the extended duration of exposure to ultrasound, whereas the expression of Bcl-2 gradually decreased. Bcl-2 expression did not differ significantly between the group exposed for 10 min and the group exposed for 20 min. Taken together, our data demonstrate that HSP70 may protect chorionic villi exposed to ultrasound by inhibiting apoptosis; however, its protective effects are limited over the extended duration of exposure to ultrasound. Thus, the prudent use of ultrasound during the early stages of pregnancy should be advocated.

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Section: Discussionmentioning

confidence: 99%

Effects of diagnostic ultrasound on HSP70 expression in chorionic villi in rats during early pregnancy and the role of HSP70 in apoptosis in chorionic villi

Liu

Hou

Liang

et al. 2013

International Journal of Molecular Medicine

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“…However, based on the immunological properties of HSPs, one could speculate that the role of HSP70 on the surface of hESCs might be associated with immune responses under certain circumstances. Actually, several studies provided evidence that immune sensitization to HSP protein is associated with unsuccessful embryo development and implantation failure in a mouse embryo culture and in vitro fertilization patients [50,51], suggesting that HSP70s are present on the surface of human and mouse embryos under certain circumstances. Because hESCs do not express the major histocompatibility complex (MHC) proteins enough before differentiation [52], it is conceivable that HSP proteins, and not MHC proteins, play a certain role in innate and adaptive immunity in hESCs during embryonic development.…”

Section: Discussionmentioning

confidence: 99%

Heat Shock 70‐kDa Protein 8 Isoform 1 Is Expressed on the Surface of Human Embryonic Stem Cells and Downregulated upon Differentiation

et al. 2005

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The cell-surface markers used routinely to define the undifferentiated state and pluripotency of human embryonic stem cells (hESCs) are those used in mouse embryonic stem cells (mESCs) because of a lack of markers directly originated from hESC itself. To identify more hESC-specific cell-surface markers, we generated a panel of monoclonal antibodies (MAbs) by immunizing the irradiated cell clumps of hESC line Miz-hES1, and selected 26 MAbs that were able to bind to Miz-hES1 cells but not to mESCs, mouse embryonic fibroblast cells, and STO cells. Most antibodies did not bind to human neural progenitor cells derived from the Miz-hES1 cells, either. Of these, MAb 20-202S (IgG1, κ) immunoprecipitated a cell-surface protein of 72-kDa from the lysate of biotin-labeled Miz-hES1 cells, which was identified to be heat shock 70-kDa protein 8 isoform 1 (HSPA8) by quadrupole time-of-flight tandem mass spectrometry.Immunocytochemical analyses proved that the HSPA8 protein was also present on the surface of hESC lines Miz-hES4, Miz-hES6, and HSF6. Two-color flow cytometric analysis of Miz-hES1 and HSF6 showed the coexpression of the HSPA8 protein with other hESC markers such as stage-specific embryonic antigen 3 (SSEA3), SSEA4, TRA-1-60, and TRA-1-81. Flow cytometric and Western blot analyses using various cells showed that MAb 20-202S specifically bound to the HSPA8 protein on the surface of Miz-hES1, contrary to other anti-HSP70 antibodies examined. Furthermore, the surface expression of the HSPA8 protein on Miz-hES1 was markedly downregulated upon differentiation. These data indicate that a novel MAb 20-202S recognizes the HSPA8 protein on the surface of hESCs and suggest that the HSPA8 protein is a putative cell-surface marker for undifferentiated hESCs. Stem Cells 2005;23:1502-1513

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“…hsp60 is one of the first proteins expressed by early-stage embryos (77). A study utilizing in vitro-cultured mouse embryos demonstrated that treatment with monoclonal antibodies to hsp60 resulted in a failure to progress (78). This established that hsp60 was present on the cell surface of early embryos and was accessible to antibody binding.…”

Section: The C Trachomatis 60-kda Heat Shock Proteinmentioning

confidence: 99%

Chlamydia trachomatis: the Persistent Pathogen

Witkin

Minis

Athanasiou

et al. 2017

Clin Vaccine Immunol

141

103

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Chlamydia trachomatis is an obligate intracellular bacterium whose only natural host is humans. Although presenting as asymptomatic in most women, genital tract chlamydial infections are a leading cause of pelvic inflammatory disease, tubal factor infertility, and ectopic pregnancy. C. trachomatis has evolved successful mechanisms to avoid destruction by autophagy and the host immune system and persist within host epithelial cells. The intracellular form of this organism, the reticulate body, can enter into a persistent nonreplicative but viable state under unfavorable conditions. The infectious form of the organism, the elementary body, is again generated when the immune attack subsides. In its persistent form, C. trachomatis ceases to produce its major structural and membrane components, but synthesis of its 60-kDa heat shock protein (hsp60) is greatly upregulated and released from the cell. The immune response to hsp60, perhaps exacerbated by repeated cycles of productive infection and persistence, may promote damage to fallopian tube epithelial cells, scar formation, and tubal occlusion. The chlamydial and human hsp60 proteins are very similar, and hsp60 is one of the first proteins produced by newly formed embryos. Thus, the development of immunity to epitopes in the chlamydial hsp60 that are also present in the corresponding human hsp60 may increase susceptibility to pregnancy failure in infected women. Delineation of host factors that increase the likelihood that C. trachomatis will avoid immune destruction and survive within host epithelial cells and utilization of this knowledge to design individualized preventative and treatment protocols are needed to more effectively combat infections by this persistent pathogen.

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Monoclonal antibodies to mammalian heat shock proteins impair mouse embryo development in vitro

Cited by 69 publications

References 22 publications

Effects of diagnostic ultrasound on HSP70 expression in chorionic villi in rats during early pregnancy and the role of HSP70 in apoptosis in chorionic villi

Effects of diagnostic ultrasound on HSP70 expression in chorionic villi in rats during early pregnancy and the role of HSP70 in apoptosis in chorionic villi

Heat Shock 70‐kDa Protein 8 Isoform 1 Is Expressed on the Surface of Human Embryonic Stem Cells and Downregulated upon Differentiation

Chlamydia trachomatis: the Persistent Pathogen

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