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Heavy Metal Cadmium Pollution Reduces the Cd14 + Subset of Blood Cells in a Chinese Population

30 Pages Posted: 3 Sep 2019

See all articles by Jingjing Cai

Jingjing Cai

Central South University - Center for Clinical Pharmacology

Yao Lu

Central South University - Center for Clinical Pharmacology

Wenduo Gu

King’s College London - British Heart Foundation (BHF) Centre of Research Excellence

Junru Wu

Central South University - Center for Clinical Pharmacology

Zhijun Huang

Central South University - Center for Clinical Pharmacology

Zhihao Shu

Central South University - Center for Clinical Pharmacology

Miao Huang

Central South University - Center for Clinical Pharmacology

Jingyuan Chen

Central South University - Center for Clinical Pharmacology

Mengli Zhou

Central South University - Center for Clinical Pharmacology

Yuanyuan Bai

Central South University - Center for Clinical Pharmacology

Xiang Chen

Central South University - Department of Dermatology

Yi Xiao

Central South University - Department of Dermatology

Minxue Shen

Central South University - Department of Social Medicine and Health Management

Dan Luo

Central South University - Department of Social Medicine and Health Management

Qihong Deng

Central South University - Xiangya School of Public Health

Liyuan Chai

Central South University - School of Materials Science and Engineering

Meian He

Huazhong University of Science and Technology - Department of Occupational and Environmental Health; Ministry of Education & Ministry of Environmental Protection, Key Laboratory of Environmental and Health; Huazhong University of Science and Technology - Key Laboratory of Environmental Health

Jicheng Gong

Peking University - College of Environmental Science and Engineering; Peking University - Beijing Innovation Center for Engineering Science and Advanced Technology (BIC-ESAT); Duke University - Nicholas School of the Environment; Duke University - Duke Global Health Institute; Duke Kunshan University

Hong Yuan

Central South University - Center for Clinical Pharmacology

Qingbo Xu

King’s College London - British Heart Foundation (BHF) Centre of Research Excellence

More...

Abstract

Background: Cadmium exposure is increasingly prevalent, especially in many developing countries, such as China. Studies have demonstrated that cadmium exposure poses a large public health threat. However, evidence for early health damage in response to cadmium exposure is still scant.

Methods: We first conducted a cross-sectional study in Hunan province, which has the highest level of cadmium land contamination in China. A total of 3,390 participants above 18 years of age were selected with cluster sampling from three districts in the Hunan region. After demographic information and blood test data were collected, a total of 3,283 subjects who met the inclusion criteria were eligible for inclusion. To screen for early health damage associated with cadmium before clinical diagnosed disease, we further excluded the individuals with hypertension, hyperlipidemia and diabetes as well as smokers and alcohol users and a total of 1,393 individuals remained. To determine which subsets of monocyte exhibit the most dramatic changes in response to cadmium exposure, 1,393 individuals were divided by plasma cadmium levels into quarters and 15 subjects were selected from the lowest and highest quartiles for single-cell RNA sequencing (scRNA-seq). Furthermore, we randomly enrolled 260 individuals from 780 subjects without chronic diseaes in Shimen district from January to March 2019 in the prospective validation study. Immunofluorescence staining for detecting CD14+ cells was performed in peripheral blood mononuclear cells (PBMCs) among the recruited individuals.

Findings: From August 2016 to July 2017, 3,283 individuals were enrolled in the cross-sectional study. The median plasma and urine cadmium levels were 0·11 μg/L and 3·94 μg/L, respectively· Among all the blood cell types examined, only the monocyte percentage was negatively associated with plasma cadmium levels (coefficient =-0·11, P=0·048) in the multivariable linear regression analysis. ScRNA-seq analysis revealed that the CD14+ monocyte subset had the most predominant reduction in the highest quartile of cadmium exposure. Both the PBMC smear analysis and flow cytometry showed that the number of CD14+ monocytes decreased significantly in subjects in the highest cadmium quartile. In the validation study, the proportion of circulating CD14+ monocytes was also negatively associated with plasma cadmium levels (coefficient =-0·09, P=0·047) by the multivariable linear regression model.

Interpretation: Cadmium exposure-associated alterations in the peripheral blood cell profile imply its effect on systemic immune surveillance and inflammatory function. This study demonstrates that the number of CD14+ monocytes is negatively associated with cadmium exposure levels and that these monocytes constitute a potential early marker for monitoring cadmium-induced health damage.

Funding Statement: National Science and Technology Project (No 2015FY111100) and the National Natural Science Foundation of China (No 81470535, 81570451, 81770403, 81870171, and 81800393).

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: The study complied with the Declaration of Helsinki, and the ethical committee of the Xiangya Hospital of Central South University and School of Public Health of Tongji Medical College of Huazhong University of Science and Technology approved the research protocol. Informed consent was obtained from the subjects or their legally authorized representatives.

Keywords: Heavy Metal, Cadmium, Immune, CD14+ Monocyte, single-cell RNA sequencing

Suggested Citation

Cai, Jingjing and Lu, Yao and Gu, Wenduo and Wu, Junru and Huang, Zhijun and Shu, Zhihao and Huang, Miao and Chen, Jingyuan and Zhou, Mengli and Bai, Yuanyuan and Chen, Xiang and Xiao, Yi and Shen, Minxue and Luo, Dan and Deng, Qihong and Chai, Liyuan and He, Meian and Gong, Jicheng and Yuan, Hong and Xu, Qingbo, Heavy Metal Cadmium Pollution Reduces the Cd14 + Subset of Blood Cells in a Chinese Population (08/25/2019 11:56:57). Available at SSRN: https://ssrn.com/abstract=3444405 or http://dx.doi.org/10.2139/ssrn.3444405

Jingjing Cai

Central South University - Center for Clinical Pharmacology

Changsha, 410013
China

Yao Lu

Central South University - Center for Clinical Pharmacology

Changsha, 410013
China

Wenduo Gu

King’s College London - British Heart Foundation (BHF) Centre of Research Excellence

London, SE5 9NU
United Kingdom

Junru Wu

Central South University - Center for Clinical Pharmacology

Changsha, 410013
China

Zhijun Huang

Central South University - Center for Clinical Pharmacology

Changsha, 410013
China

Zhihao Shu

Central South University - Center for Clinical Pharmacology

Changsha, 410013
China

Miao Huang

Central South University - Center for Clinical Pharmacology

Changsha, 410013
China

Jingyuan Chen

Central South University - Center for Clinical Pharmacology

Changsha, 410013
China

Mengli Zhou

Central South University - Center for Clinical Pharmacology

Changsha, 410013
China

Yuanyuan Bai

Central South University - Center for Clinical Pharmacology

Changsha, 410013
China

Xiang Chen

Central South University - Department of Dermatology

Changsha
China

Yi Xiao

Central South University - Department of Dermatology

Changsha
China

Minxue Shen

Central South University - Department of Social Medicine and Health Management

Changsha
China

Dan Luo

Central South University - Department of Social Medicine and Health Management

Changsha
China

Qihong Deng

Central South University - Xiangya School of Public Health ( email )

Changsha
China

Liyuan Chai

Central South University - School of Materials Science and Engineering

Changsha, Hunan 410083
China

Meian He

Huazhong University of Science and Technology - Department of Occupational and Environmental Health ( email )

13 Hangkong Rd
Wuhan, 430030
China

Ministry of Education & Ministry of Environmental Protection, Key Laboratory of Environmental and Health ( email )

Wuhan
China

Huazhong University of Science and Technology - Key Laboratory of Environmental Health ( email )

Wuhan, 430030
China

Jicheng Gong

Peking University - College of Environmental Science and Engineering

Beijing, 100080
China

Peking University - Beijing Innovation Center for Engineering Science and Advanced Technology (BIC-ESAT)

Beijing, 100871
China

Duke University - Nicholas School of the Environment

9 Circuit Dr.
Environment Hall
Durham, NC 27708
United States

Duke University - Duke Global Health Institute

310 Trent Drive
Box 90519
Durham, NC 27710
United States

Duke Kunshan University

No. 8 Duke Avenue
Kunshan, Jiangsu 215316
China

Hong Yuan

Central South University - Center for Clinical Pharmacology

Changsha, 410013
China

Qingbo Xu (Contact Author)

King’s College London - British Heart Foundation (BHF) Centre of Research Excellence ( email )

London, SE5 9NU
United Kingdom