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Heme concentration-dependently modulates the production of specific antibodies in murine

Guofu Li, Haiyan Xue, Zeng Fan, Yun Bai
doi: https://doi.org/10.1101/071316
Guofu Li
School of Life Sciences, Sun Yat-Sen University, Guangzhou, China, 510275
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  • For correspondence: lsslgf@mail.sysu.edu.cn
Haiyan Xue
School of Life Sciences, Sun Yat-Sen University, Guangzhou, China, 510275
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Zeng Fan
School of Life Sciences, Sun Yat-Sen University, Guangzhou, China, 510275
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Yun Bai
School of Life Sciences, Sun Yat-Sen University, Guangzhou, China, 510275
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Abstract

Free heme is an endogenous danger signal to provoke innate immunity. Active innate immunity is a precondition of an effective adaptive immune response. However, heme catabolites, CO, biliverdin and bilirubin trigger immunosuppression. Furthermore, free heme induces the expression of heme oxygenase-1 to reinforce the production of CO, biliverdin and bilirubin. As such, free heme can drive two antagonistic mechanisms to affect adaptive immunity. What is the outcome of animal immune response to an antigen in the presence of free heme? The question remains to be explored. Here we report the immunization results by intraperitoneal injection of the formulations containing BSA and heme. When the used heme concentrations were about less than 1 µM, the production of anti-BSA IgG and IgM was unaffected; when the used heme concentrations were about more than 1 µM but less than 5 µM, the production of anti-BSA IgG and IgM was enhanced; when the used heme concentrations were about more than 5 µM, the production of anti-BSA IgG and IgM was suppressed. The results demonstrate that heme can modulate adaptive immunity (at least humoral immunity) by the mode of double concentration-thresholds. If heme concentrations are below the first threshold, there is no effect on adaptive immunity; if between the first and second thresholds, there is promotive effect; if over the second threshold, there is inhibitive effect. A hypothesis is also presented here to explain the mode.

Abbreviations
CFA
Complete Freund’s adjuvant
DAMP
damage associated molecular pattern
PAMP
pathogen-associated molecular pattern
HO
heme oxygenase
HEcL
human erythrocyte lipid
REcL
rat erythrocyte lipid
LREcL
hemolytic rat erythrocyte lipid
LPS
Lipopolysaccharide
PC
phosphatidylcholine
ROS
reactive oxygen species
TLR
Toll-like receptor
Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 24, 2016.
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Heme concentration-dependently modulates the production of specific antibodies in murine
Guofu Li, Haiyan Xue, Zeng Fan, Yun Bai
bioRxiv 071316; doi: https://doi.org/10.1101/071316
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Heme concentration-dependently modulates the production of specific antibodies in murine
Guofu Li, Haiyan Xue, Zeng Fan, Yun Bai
bioRxiv 071316; doi: https://doi.org/10.1101/071316

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