Many specific therapeutic antibody drugs have been developed for different indications. In drug development, it has been found that the antibody isotype framework can not only affect the physical and chemical properties of therapeutic antibodies, but also influence the activity and therapeutic effect. As a result, IgG isotype selection should be considered carefully in antibody drug development strategies. Because of the unique biological characteristics, IgG4 isotype has been used in some therapeutic antibodies for which effector functions are not desired. In order to provide new ideas for the development of antibody drugs, the research and application progress of IgG4 isotype in therapeutic antibody drug development has been reviewed.
Drug Design ; Humans ; Immunoglobulin G ; chemistry ; pharmacology

Snake antivenomimmunoglobulins are considered to be the most efficient drugs in snake envenomings. Most snake antivenomimmunoglobulins all over the world are still prepared by fragmentation of polyclonal antibodies isolated from hyper-immunized horse serum till now. In this review, we retrospect the history of snake antivenomimmunoglobulins, analysis the present situation and pay the close attention on the key technological links in the process of research and manufacturing, such as properties of IgG and its fragments, selection and preparation of immunogen, optimization of immunization schedule and protein isolation and purification, which can be available for the reference in the research and development of snake antivenom.
Animals ; Antivenins ; pharmacology ; Humans ; Immunoglobulin G ; pharmacology ; Snake Bites ; drug therapy ; Snakes

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.
Cellular Senescence/genetics* ; Humans ; Immunoglobulin G/metabolism* ; Interleukin-13/pharmacology* ; Mitochondria/metabolism* ; Sialadenitis/metabolism*

OBJECTIVETo examine the effect of aqueous extracts of Scutellaria baicalensis Georgi and Radix paeoniae Alba on periodontitis mice and compare the results of the two herbs for the treatment of the periodontitis mice.

METHODSSixty-four SPF 12-week-old male Kunming mice were selected and randomly divided into four groups:Control group(C); Experimental periodontitis group (P):the peridontitis models in Kunming mice were prepared by wrapping silk ligature and inoculating with putative periodontopathic bacteria; Scutellaria baicalensis Georgi treatment group (SG): periodontitis was induced by the same method described above, the mice were gavaged with Scutellaria baicalensis Georgi; Radix paeoniae Alba treatment group (RG): periodontitis was induced by the same method described above, the mice were gavaged with Radix paeoniae Alba.Four mice were sacrificed at each time point of the end of 4, 6, 8 and 10 weeks in each group. The histopathological changes of periodontal tissue were observed under microscope with HE staining. The level of serum IgG1 and IgG2a was measured by enzyme-linked immunosorbent assay (ELISA) .

RESULTSA serious inflammatory response, alveolar progressive absorption and a large number of osteoclasts were observed in the experimental periodontitis group.However, in SG and RG, the inflammation of the periodontal tissue was decreased and tissue repair was significant. The level of serum IgG2a in SG (6 week:0.934 ± 0.006, 8 week:0.743 ± 0.009, 10 week: 0.674 ± 0.008) and RG (6 week: 1.023 ± 0.032, 8 week: 0.851 ± 0.032, 10 week:0.790 ± 0.009) was significantly decreased after the mice were gavaged with the two herbs(P < 0.01). The level of serum IgG2a in SG was significantly lower than that of RG (P < 0.01). The level of serum IgG1 in SG (6 week: 0.314 ± 0.006, 8 week: 0.344 ± 0.004, 10 week: 0.367 ± 0.006) and RG (6 week: 0.287 ± 0.005, 8 week: 0.303 ± 0.058, 10 week: 0.336 ± 0.006) were significantly increased (P < 0.01). The level of serum IgG1 in SG was significantly higher than that of RG (P < 0.01).

CONCLUSIONSBoth the aqueous extracts of Scutellaria baicalensis Georgi and Radix paeoniae Alba showed therapeutic effect on periodontitis in mice.Scutellaria baicalensis Georgi was more effective than Radix paeoniae Alba.

Aconitum ; Animals ; Immunoglobulin G ; metabolism ; Male ; Mice ; Paeonia ; Periodontitis ; metabolism ; Plant Extracts ; pharmacology ; Scutellaria baicalensis ; Water

The experiment was conducted to prepare chitosan nanoparticles (CNP), to entrap VRMIL-2 with CNP, the eukaryotic VR1020 expression plasmid containing murine IL-2 gene (mlL-2), and to investigate the expression in vivo and the regulatory effect of mIL-2 on immune-response and immuno-protection in mice inoculated muscularly with CNP entrapped VMIL-2 at 21 days old. The results showed that IgG, IgM and IgA contents increased to different degrees in the sera from the inoculated mice, which were remarkably higher than those of the controls inoculated VR1020 packed with CNP (P<0.05); so were the IL-2, IL-4 and IL-6 contents in the sera of the immunized mice. The number of white blood cells and lymphocytes significantly increased respectively in the vaccinated mice, compared with those of controls. These mice were orally challenged with virulent E. coli 35 days post-inoculation, and all the immune responses were significantly higher than those of the control except the number of neutrophils. The mice inoculated with VRMIL-2 survived healthily, while the mice of control group were ill with the evident lesions. Although there are no remarkable differences between the cellular and humoral immune indexes of mice inoculated with CNP-VRMIL-2 and nude VRMIL-2 (P>0.05), the dosage of CNP-VRMIL-2 is only one fifth of the VRMIL-2. These indicated that entrapment of mIL-2 gene with chitosan nanoparticles could remarkably enhance the expression of mIL-2 in vivo, and significantly raise the levels of cellular and humoral immune, and increase the resistance of mice against E. coli infection. The results suggested that chitosan nanoparticles and IL-2 gene could be used as an effective immunoenhancer to increase the immunity of animals against infection.
Adjuvants, Immunologic ; pharmacology ; Animals ; Chitosan ; pharmacology ; Escherichia coli Infections ; immunology ; prevention & control ; Female ; Immunoglobulin G ; blood ; Interleukin-2 ; biosynthesis ; genetics ; pharmacology ; Mice ; Nanostructures

Cationic PLG nanoparticles and liposome were prepared and used as package molecules to pack up pUC18-CpG. The effects of the packed pUC18-CpG on the cellular and humoral immune responses were detected in the mice that were inoculated with pig paratyphoid vaccine. The results showed that compared with the control, the amount of IgG and the titre of specific antibody were significantly increased in the sera of mice immunized with the CpG plasmid entrapped by cationic PLG nanoparticles; the proliferation and induced IL-2 bioactivity of lymphocytes were significantly enhanced in the spleen of the immunized mice; the stimulatory effect of cationic PLG nanoparticles was similar to or stronger than that of cationic liposome. These indicated that cationic PLG nanoparticle could be employed as an effective package molecule to promote the immunostimulatory effect of pUC18-CpG.
Adjuvants, Immunologic ; pharmacology ; Animals ; Immunoglobulin G ; blood ; Interleukin-2 ; blood ; Liposomes ; Male ; Mice ; Mice, Inbred BALB C ; Nanostructures ; Oligodeoxyribonucleotides ; pharmacology ; Swine ; Typhoid-Paratyphoid Vaccines ; immunology

OBJECTIVETo study the effects of the Rich Selenium-Banqiao-Codonopsis Pilosula (BCPA) injecta on the aged rats' immune functions and its underlying mechanism.

METHODSTotally 60 rats, composed of 2, 12 and 22 month age old (half male and half female), were served as a young group, middle-age group and aged group respectively. Each group rats were randomly divided into the control and the BCPA subgroup (n = 10). The BCPA group was injected with BCPA at 7.2 g/kg intraperitoneally every day and the control group was injected the same volume of normal saline. All rats were conventionally fed for 45 days. An immune injection was performed after 15 days of BCPA injection. On the 22nd day, late-onset immune response would be induced. The caudal vein blood was collected and the antigen specific IgG, IgG1 and IgG2a antibody was detected on the 15th, 30th and 45th day. On the 45th day, the major T cell subgroups of splenic cells were analyzed and splenic cells were proliferated.

RESULTSNo significant difference in the delayed-type hypersensivity (DTH) reaction was found between the control and the BCPA subgroups in the young and middle-aged rats while the aged BCPA subgroup had a stronger DTH reaction. There was no significant difference in the blood content of specific IgG, IgG1 and IgG2a antibody between the young and middle-age BCPA group while the aged BCPA group rats had an obvious enhancing reaction to the three antibodies mentioned above (P < 0.05). There was no obvious difference in the number of the CD3+ lymphocytes and the CD4+ T helper lymphocytes between the control and the BCPA subgroup in the young aged rats while a significant increase was spotted between the middle-aged and the aged group (P < 0.05). The splenic cells from young BCPA group rats had a strong proliferation response (P < 0.05).

CONCLUSIONBCPA can enhance DTH reaction, potentiate the production of specific IgG, IgG1 and IgG2a antibody to resist KLH, improve the reaction to antigen, increase the amount of CD4+ cell, promote the immune response and had an important role in anti-immunosenescence and antioxidant capacity improvement in the aged rats.

Aging ; Animals ; CD4-Positive T-Lymphocytes ; immunology ; Codonopsis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Female ; Immune System ; drug effects ; Immunoglobulin G ; blood ; Male ; Rats ; Selenium ; pharmacology ; Spleen ; immunology

OBJECTIVETo study the effect of exogenous cytokine-stimulated decidual cells on IgG secretion of B lymphocytes and investigate the features of local immunological microenvironment of the decidua.

METHODSExogenous cytokines interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-6 and epidermal growth factor (EGF) were added separately in cultured decidual cells, and the supernatant of the culture medium was prepared for stimulating human peripheral blood lymphocytes. IgG secretion of the B cells was measured by radio-immunological method.

RESULTThe decidual cells of normal early pregnancy stimulated B lymphocyte IgG secretion, and the supernatant of exogenous cytokine-stimulated decidual cells had the same effect, which, however, was depended not on the concentration and category of the cytokines, but only on the time of treatment.

CONCLUSIONThe exogenous cytokines can increase the humoral immunity in the decidual immunological microenvironment, but such effect might result from a self-regulatory mechanism of the local immunological microenvironment of the decidua, which can be fundamental for maintenance of normal pregnancy.

Adult ; B-Lymphocytes ; cytology ; drug effects ; metabolism ; Cells, Cultured ; Culture Media, Conditioned ; pharmacology ; Cytokines ; pharmacology ; Decidua ; cytology ; drug effects ; metabolism ; Female ; Humans ; Immunoglobulin G ; biosynthesis ; Interferon-gamma ; pharmacology ; Interleukin-2 ; pharmacology ; Pregnancy ; Pregnancy Trimester, First

To establish a better method of primary culture for alveolar epithelial type II cells (AEC II) and to study its bionomics, alveolar epithelial type II cells were isolated by digestion with trypsin and collagenase, which were then purified by plated into culture flask coated with rat immunoglobulin G. The purified AEC II were identified by alkaline phosphatase staining, electron microscopy, immunocytochemical staining of pulmonary surfactant protein A (SPA). The SPA expression and transfection characteristics were compared with those of A549 cell line. The results showed that AEC II could be isolated by digestion with trysin and collagenase and purified by adhesive purification by using IgG, with a yield of about 2-3 x 10(7), and a purity of about 75%-84%. Cells could be quickly identified with AKP staining. AEC II were different from A549 cell line in terms of SPA expression and transfection characteristics. It is concluded that adhesive purification with IgG can improve the purity of AEC II, and AKP staining is simple in cell identification. AEC II can not be completely replaced by A549 cells in some studies because the differences between them, such as SPA expression.
Cell Culture Techniques/*methods ; Cell Separation/*methods ; Cells, Cultured ; Ecology ; Epithelial Cells/*cytology ; Immunoglobulin G/pharmacology ; Pulmonary Alveoli/*cytology ; Pulmonary Surfactant-Associated Protein A/biosynthesis ; Rats, Wistar

Animals ; Concanavalin A ; adverse effects ; Immunoglobulin G ; blood ; Interleukin-18 ; blood ; immunology ; pharmacology ; Liver Cirrhosis ; blood ; chemically induced ; prevention & control ; Mice ; Mice, Inbred BALB C