Journal of Immunotoxicology最新文献

{"title":"Expression and clinical significance of the m6A reader <i>YTHDF2</i> in peripheral blood mononuclear cells from rheumatoid arthritis patients.","authors":"Fangyi Yao,&nbsp;Chuxin Xu,&nbsp;Yujie Gao,&nbsp;Biqi Fu,&nbsp;Lu Zhang,&nbsp;Yang Guo,&nbsp;Zikun Huang,&nbsp;Xiaozhong Wang,&nbsp;Junming Li,&nbsp;Qing Luo","doi":"10.1080/1547691X.2022.2067916","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2067916","url":null,"abstract":"Abstract As an important m6A reader, the YT521-B homology domain family 2 (YTHDF2) has been shown to regulate mRNA degradation and translation, and to be involved in inflammation. However, little is known about the role of YTHDF2 in the autoimmune-based inflammatory disease rheumatoid arthritis (RA). To begin to ascertain any role for this reader, 74 RA patients and 63 healthy controls (HC) were recruited for this study. Blood was collected from each subject and peripheral blood mononuclear cells (PBMC) isolated. Thereafter, mRNA expression of YTHDF2, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in the cells was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The harvested blood was also assessed for a variety of parameters, including levels of C-reactive protein (CRP), erythrocyte sedimentation rates (ESR), white blood cell counts (WBC), neutrophils counts (N)/neutrophils percentages (N%), and neutrophil:lymphocyte ratios (NLR) - each markers of inflammation during RA. The results showed that YTHDF2 mRNA expression in RA patient PBMC was decreased significantly vs that in healthy control subject cells. Further, YTHDF2 mRNA expression in RA patient PBMC negatively-correlated with ESR, CRP levels, WBC counts, as well as neutrophils counts, percentages, and NLR values. In addition, it was seen that YTHDF2 mRNA expression in RA patient PBMC was associated with host serum RF levels and treatment. Moreover, it was found that mRNA expression of IL-1β, IL-6, IL-8, and TNFα was increased in PBMC from RA patients relative to in control subject cells; however, only the increased IL-1β expression was seen to be negatively-correlated with decreased YTHDF2 mRNA expression. In conclusion, the present study illustrated that YTHDF2 expression might have some regulatory role in the underlying mechanisms associated with the autoimmune disease RA and that this m6A reader could at some point represent a potential target for regulating inflammatory responses that occur during RA.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"53-60"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10408016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bisphenol A, T_H17 cells, and allergy: a commentary.","authors":"Ian Kimber,&nbsp;Nicole Woeffen,&nbsp;Kevin Sondenheimer","doi":"10.1080/1547691X.2022.2113842","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2113842","url":null,"abstract":"<p><p>There is a continuing interest in whether Bisphenol A (BPA) is able to cause adverse health effects through interaction with elements of the immune system. That interest has been fuelled further by the recent publication of a draft opinion on BPA prepared by the European Food Safety Authority (EFSA) Panel on Food Contact Materials, Enzymes and Processing Aids (CEP). This draft opinion judged effects on the immune system to be the most sensitive health outcome, and identified BPA-induced changes in the frequency of T-helper (T_H)-17 cells in the spleens of mice as being the critical effect based on an association of these cells with inflammation. Based on these evaluations the CEP Panel recommended that a revised Tolerable Daily Intake (TDI) for BPA of 0.04 ng/kg bw/day should be adopted; representing a very substantial reduction (100,000-fold) compared with the existing TDI. The purpose of this commentary is to summarize briefly the role of T_H17 cells in immune responses, and to review relevant literature regarding the influence of BPA on these cells, and on inflammatory responses in the lung and respiratory allergy. The conclusion drawn is that based on uncertainties about the effects of BPA on T_H17 cells and lung inflammation in mice, the absence of consistent or persuasive evidence from human studies that exposure of BPA is associated with inflammation or allergy, and unresolved questions regarding the species selectivity of immune effects induced by BPA, it is inappropriate to adopt the revised TDI. Additional research is required to explore further the influence of BPA on the immune system and immune responses.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"93-99"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10417275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A T-cell-dependent antibody response (TDAR) method in BALB/c mice based on a cytometric bead array","authors":"Wenhua Zhong, Penghuan Chang, Lianfang Gan, Lifan Zhong, Zhaoxin Yang","doi":"10.1080/1547691X.2022.2067273","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2067273","url":null,"abstract":"Abstract Most current methods to assess T-cell-dependent antibody responses (TDAR) are semi-quantitative and based on measures of antibody titer generated against a standard antigen like keyhole limpet hemocyanin (KLH). The precision, sensitivity, and convenience of TDAR assays might be improved by applying rapid, sensitive, specific cytometric bead assays (CBA). In the study here, KLH antigen was covalently coupled onto the surface of cytometric beads using immune microsphere technology, and IgM antibody capture spheres were prepared for use in pretreatment processing of samples. The working parameters associated with this novel TDAR-CBA system were optimized in orthogonal experiments. The optimal concentration of the KLH coating solution in this system was 160 μg/ml, that of the anti-KLH IgG capture spheres 6.0 × 105/ml, and the optimal dilution of fluorescein isothiocyanate (FITC)-conjugated Affini-Pure Goat Anti-Mouse IgG (H + L) was 60 μg/ml. Repeated tests indicated that this approach yielded good linearity (r 2 = 0.9937) method, with a within-run precision of 3.1–4.9%, and a between-run precision of 4.4–4.9%. This new approach had a limit of detection of 113.43 ng/ml (linear range = 390.63–50 000), and an interference rate of just 0.04–3.51%. Based on these findings, it seems that a new mouse TDAR assay based on CBA can be developed that would appear to be more sensitive, accurate, and precise than the current TDAR assay approaches based on traditional ELISA.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"34 - 40"},"PeriodicalIF":3.3,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43203050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteolytic activity accelerates the TH17/TH22 recall response to an epicutaneous protein allergen-induced TH2 response","authors":"A. Ogasawara, T. Yuki, Asuka Katagiri, Yi-Ting Lai, Yutaka Takahashi, D. Basketter, H. Sakaguchi","doi":"10.1080/1547691X.2022.2049665","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2049665","url":null,"abstract":"Abstract Epicutaneous exposure to protein allergens, such as papain, house dust mite (HDM), and ovalbumin (OVA), represents an important mode of sensitization for skin diseases including protein contact dermatitis, immunologic contact urticaria, and atopic dermatitis. These diseases are inducible by re-exposure to an allergen at both original skin sensitization and distant skin sites. In this study, we examined the serum IgE/IgG1 response, differentiation of T-helper (TH) cells, and epicutaneous TH recall response in mice pre-sensitized with protein allergens through the back skin and subsequently challenged on the ear skin. Repeated epicutaneous sensitization with allergenic proteins including papain, HDM, OVA, and protease inhibitor-treated papain, but not bovine serum albumin, induced serum allergen-specific antibody production, passive cutaneous anaphylaxis responses, and TH2 differentiation in the skin draining lymph node (DLN) cells. Sensitization with papain or HDM, which have protease activity, resulted in the differentiation of TH17 as well as TH2. In papain- or HDM-sensitized mice, a subsequent single challenge on the ear skin induced the expression of TH2 and TH17/TH22 cytokines. These results suggest that allergenic proteins induce the differentiation of TH2 in skin DLN cells and an antibody response. These findings may be useful for identifying proteins of high and low allergenic potential. Moreover, allergenic proteins containing protease activity may also differentiate TH17 and induce TH2 and TH17/TH22 recall responses at epicutaneous challenge sites. This suggests that allergen protease activity accelerates the onset of skin diseases caused by protein allergens.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"27 - 33"},"PeriodicalIF":3.3,"publicationDate":"2022-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43805967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gallic acid attenuates cerebral ischemia/re-perfusion-induced blood–brain barrier injury by modifying polarization of microglia","authors":"Yang Qu, Lin Wang, Yanfang Mao","doi":"10.1080/1547691X.2022.2043494","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2043494","url":null,"abstract":"Abstract Microglia, the main immune effector cells in the central nervous system, play a dual role in the function/structure of the blood–brain barrier (BBB) and brain health. During and soon after a cerebral ischemic injury, microglia produce neurotrophic factors and neurotoxins that can impact on the injury itself and pathology progression. At the same time, microglia undergo polarization to M1 or M2 pro- vs. anti-inflammatory subtypes that also help drive the outcome of the injury process. Thus, agents that can mitigate cerebral ischemic injury progression, promote protective functions of microglia, and help maintain BBB and overall brain health/host neurologic function after a cerebral ischemic event would be of great use in clinical settings. Protective effects from gallic acid (GA) in cerebral ischemia/re-perfusion-induced injury to the BBB and other sites in the brain have not yet been assessed. To address this, a middle cerebral artery occlusion (MCAO) method was used to establish an experimental ischemic stroke model in mice. Mice were placed in sham operation (Sham), model (MCAO), MCAO + GA (50 mg/kg), MCAO + GA (100 mg/kg), or MCAO + GA (150 mg/kg) groups. At various times post-stroke, cerebral infarct volume and host neurological function were evaluated. In addition, qRT-PCR, Western blotting, and ELISA were used to evaluate the expression and tissue content of microglia-related factors. The results showed GA treatment protected the integrity of the BBB, significantly reduced brain edema, and helped lead to improved neurological function scores in the MCAO mice. Whether these changes were due to that GA attenuated cerebral ischemia/re-perfusion-induced activation of microglial cells overall, in part, by inhibiting their polarization to the M1 subtype, is uncertain. Taking these outcomes together, for now it is reasonable to suggest that use of GA either as a prophylactic or immediately in the event of a cerebral ischemic event/stroke could help to promote neuronal survival and allow for a more likely of host neurological function over time.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"17 - 26"},"PeriodicalIF":3.3,"publicationDate":"2022-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"59983522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical stress quickly affects the numbers of circulating B-cells and neutrophils in murine septic and aseptic models through a β2 adrenergic receptor","authors":"R. Nishioka, Y. Nishi, Mohammed E. Choudhury, Riko Miyaike, Ayataka Shinnishi, K. Umakoshi, Yasutsugu Takada, Norio Sato, M. Aibiki, Hajime Yano, Junya Tanaka","doi":"10.1080/1547691X.2022.2029630","DOIUrl":"https://doi.org/10.1080/1547691X.2022.2029630","url":null,"abstract":"Abstract Sepsis is a pathology accompanied by increases in myeloid cells and decreases in lymphoid cells in circulation. In a murine sepsis model induced by cecum ligation and puncture (CLP), increasing numbers of neutrophils and decreasing levels of B-cells in circulation are among the earliest changes in the immune system. However, to date, the mechanisms for these changes remain to be elucidated. The study here sought to elucidate mechanisms underlying the changes in the leukocyte levels after CLP and also to determine what, if any, role for an involvement of the sympathetic nervous system (SNS). Here, male C57/BL6 mice were subjected to CLP or sham-CLP (abdominal wall incised, but cecum was not punctured). The changes in the number of circulating leukocytes over time were then investigated using flow cytometry. The results showed that a sham-CLP led to increased polymorphonuclear cells (PMN; most of which are neutrophils) and decreased B-cells in the circulation to an extent similar to that induced by CLP. Effects of adrenergic agonists and antagonists, as well as of adrenalectomy, were also examined in mice that underwent CLP or sham-CLP. Administering adrenaline or a β2 adrenergic receptor agonist (clenbuterol) to mice 3 h before sacrifice produced almost identical changes to as what was seen 2 h after performing a sham-CLP. In contrast, giving a β2 adrenergic receptor antagonist ICI118,551 1 h before a CLP or sham-CLP suppressed the expected changes 2 h after the operations. Noradrenaline and an α1 adrenergic receptor agonist phenylephrine did not exert significant effects. Adrenalectomy 24 h before a sham-CLP significantly abolished the expected sham-CLP-induced changes seen earlier. Clenbuterol increased splenocyte expression of Cxcr4 (a chemokine receptor gene); adrenalectomy abolished sham-CLP-induced Cxcr4 expression. A CXCR4 antagonist AMD3100 repressed the sham-CLP-induced changes. From these results, it may be concluded that sepsis-induced activation of the SNS may be one cause for immune dysfunction in sepsis – regardless of the pathogenetic processes.","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"19 1","pages":"8 - 16"},"PeriodicalIF":3.3,"publicationDate":"2022-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42996302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly sensitive <i>in vitro</i> cytokine release assay incorporating high-density preculture.","authors":"Shiho Ito,&nbsp;Kyoko Miwa,&nbsp;Chiharu Hattori,&nbsp;Tetsuo Aida,&nbsp;Yoshimi Tsuchiya,&nbsp;Kazuhiko Mori","doi":"10.1080/1547691X.2021.1984617","DOIUrl":"https://doi.org/10.1080/1547691X.2021.1984617","url":null,"abstract":"<p><p>Immunostimulatory effects of monoclonal antibodies (mAb) through binding to F_cγ receptors (F_cγR) on immune cells are a likely cause of cytokine release syndrome. However, it is difficult to detect the potential risk of F_cγR-dependent cytokine release associated with mAb in the current standard cytokine release assays (CRA), including the air-drying solid-phase method using human peripheral blood mononuclear cells (PBMC). To increase the sensitivity to detect F_cγR-dependent cytokine release due to mAb, a high-density preculture (HDC) method was incorporated into the air-drying solid-phase CRA. Here, PBMC were exposed to panitumumab, trastuzumab, rituximab, or alemtuzumab at 0.1, 0.3, 1, and 3 μg/well for 24 or 48 hr under both non-HDC and HDC conditions. T-cell agonists (anti-CD3 mAb, anti-CD28 super-agonist [SA] mAb) were used as reference mAb. Panitumumab, trastuzumab, rituximab, or alemtuzumab induced cytokine release under both non-HDC and HDC conditions, and cytokine release caused by alemtuzumab was more pronounced under HDC conditions. To investigate F_cγR involvement in cytokine release associated with panitumumab, trastuzumab, rituximab, and alemtuzumab, CRA of these four mAb were conducted with anti-F_cγRI, -F_cγRII, or -F_cγRIII F(ab')₂ fragments. The results showed cytokine release caused by trastuzumab, rituximab, and alemtuzumab was significantly suppressed by anti-F_cγRIII F(ab')₂ pretreatment, and slightly reduced by anti-F_cγRI or anti-F_cγRII pretreatment, indicating these mAb induced F_cγR (especially F_cγRIII)-dependent cytokine release from PBMC. Cytokine release caused by panitumumab was slightly suppressed by anti-F_cγRIII F(ab')₂ pretreatment. Anti-CD3 mAb and anti-CD28 SA mAb also induced significant release of cytokines under HDC conditions compared with that under non-HDC conditions. In conclusion, CRA incorporating HDC into the air-drying solid-phase method using human PBMC could sensitively capture the F_cγR-dependent cytokine release potential of mAb.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"136-143"},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39515293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of injection buffer volume to perform bronchoalveolar lavage fluid collection for isolating alveolar macrophages to investigate fine particle-induced IL-1α secretion.","authors":"Eita Sasaki,&nbsp;Haruka Momose,&nbsp;Keiko Furuhata,&nbsp;Takuo Mizukami,&nbsp;Isao Hamaguchi","doi":"10.1080/1547691X.2021.1979699","DOIUrl":"https://doi.org/10.1080/1547691X.2021.1979699","url":null,"abstract":"<p><p>The importance of alveolar macrophages has been reported in many toxicology/immunology studies. Alveolar macrophages release interleukin (IL)-1α as a damage-associated molecular pattern (DAMP) when stimulated by fine particles. However, it is unclear whether cell isolation procedures affect <i>ex vivo</i> particle-induced responses in primary mouse alveolar macrophages (mAM). In this study, effects of injection buffer volume used to perform bronchoalveolar lavage fluid (BALF) collection to isolate mAM for use in <i>ex vivo</i> particle-induced responses were assessed. Among the mAM obtained from BALF collected using a 0.55 or 0.75 ml, but not a 1.0 ml buffer injection volume, decreased cell viability and IL-1α release were observed when cells were stimulated <i>ex vivo</i> with silica crystal or aluminum salt. Injected buffer composition did not affect the IL-1α release. On the other hand, IL-6 secretion induced by lipopolysaccharide (LPS) did not differ among mAM obtained from BALF collected using the different volumes. Expression levels of cell surface markers like CD11c, SiglecF, and CD64 did not differ among mAM obtained from BALF collected using the different injection buffer volumes. IL-1α release (and also necroptosis) induced by <i>ex vivo</i>particle stimulation was suppressed by RIPK3 inhibitor or cytochalasin D co-treatment. Decreases in RIPK3 phosphorylation were noted in mAM obtained in BALF collected using the 1.0 ml injection volume compared with mAM obtained in BALF using 0.55 or 0.75 ml buffer. These observations illustrate that larger volumes of buffer used to collect BALF from mice can affect sensitivity of the isolated mAM to <i>ex vivo</i> particle-induced responses by inhibiting their functions.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"163-172"},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39863816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal tubular cell necroptosis: A novel mechanism of kidney damage in trichloroethylene hypersensitivity syndrome mice.","authors":"Yican Wang,&nbsp;Meng Huang,&nbsp;Xin Du,&nbsp;Yiting Hong,&nbsp;Liping Huang,&nbsp;Yuying Dai,&nbsp;Qifeng Wu,&nbsp;Feng Wang,&nbsp;Qixing Zhu","doi":"10.1080/1547691X.2021.2003486","DOIUrl":"https://doi.org/10.1080/1547691X.2021.2003486","url":null,"abstract":"<p><p>Trichloroethylene (TCE) hypersensitivity syndrome (THS), called occupational medicamentosa-like dermatitis due to TCE (OMDT) in China, is a fatal occupational disorder caused by TCE exposure. Visceral damage, including kidney injury, is one of the major complications. Necroptosis is a regulated cell death form linked to local inflammatory response. This study aimed to investigate whether renal cell necroptosis was involved in TCE-induced kidney injury. A Balb/c mouse model of TCE sensitization was utilized to study mechanisms of modulation of TCE-induced renal necroptosis. Renal histology (using light and transmission electron microscopy) and renal tubular impairment indexes, including α1-microglobulin (α1-MG), and β2-microglobulin (β2-MG), were evaluated. In addition, tissue expression of necroptosis-related proteins, including tumor necrosis factor (TNF)-α, TNF receptor 1 (TNFR1), receptor-interacting protein kinase 3 (RIPK3), p-RIK3, mixed lineage kinase domain-like protein (MLKL), and p-MLKL, were also evaluated. The study here confirmed TCE sensitization caused damage to renal tubules and renal tubular epithelial cell (RTEC) necroptosis. In mice treated with R7050 (a specific TNFα antagonist), it was also seen that inhibition of TNFα expression could effectively inhibit RTEC necroptosis and improve renal function in the TCE-sensitized mice. Taken together, these results help to define a novel mechanism by which RTEC necroptosis plays a key role in TCE-induced kidney damage.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"173-182"},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39898939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A T-dependent antibody response evaluation in CD-1 mice after an acute whole-body inhalation exposure to nickel (II) chloride hexahydrate.","authors":"Samuel Buxton,&nbsp;Michael D Taylor,&nbsp;Jeffrey T Weinberg,&nbsp;James M Randazzo,&nbsp;Vanessa L Peachee,&nbsp;Adriana Oller","doi":"10.1080/1547691X.2021.1984618","DOIUrl":"https://doi.org/10.1080/1547691X.2021.1984618","url":null,"abstract":"<p><p>Nickel (Ni) in ambient air may vary regionally with contributions from both natural processes and anthropogenic activities. Exposure to Ni compounds in ambient air above a certain level is associated with acute adverse effects, such as upper respiratory tract irritation, pneumonitis, and chronic adverse effects, such as respiratory cancer. Inhalation reference exposure standards are enacted in different jurisdictions to minimize exposures to ambient Ni above levels that can elicit adverse effects. This paper reports a guideline-/GLP-compliant study designed for setting inhalation exposure standards to protect from immunological effects associated with acute exposure to Ni. Female CD-1 mice were exposed via whole-body inhalation to aerosolized nickel chloride hexahydrate for 24-hr at nominal (vs. mean analyzed) concentrations of 20 (16), 50 (44) and 100 (81) µg Ni/m³. Host T-cell antibody immunological responses to intravenously-injected sheep red blood cells were then measured <i>ex vivo</i> in an Antibody-Forming Cell (AFC) assay. Exposure to the Ni substance significantly decreased spleen cell levels by 33%, but this was within biological variability for outbred mice. No concurrent decreases in spleen, thymus, or body weights were noted. No immunosuppression was observed with the Ni substance in the context of Total Spleen Activity [IgM AFC/spleen (× 10³)] and Specific Activity [IgM AFC/spleen cells (× 10⁶)]. Significant concentration-independent increases in Total Spleen Activity and Specific Activity seen with the nickel chloride hexahydrate were normal and within biological variability for outbred mice. In contrast, cyclophosphamide (positive control) significantly decreased spleen cell numbers, spleen and thymus weights, and abolished Specific Activity and Total Spleen Activity. Based on results here, an NOAEC of 81 µg Ni/m³ for immunosuppressive effects from inhaled nickel chloride hexahydrate was identified. It is hoped this value can be used to derive a reference standard for human exposure to ambient Ni.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"144-153"},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39539330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}