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The Human Monocyte-A Circulating Sensor of Infection and a Potent and Rapid Inducer of Inflammation

Lara, Sandra and Akula, Srinivas and Fu, Zhirong and Olsson, Anna-Karin and Kleinau, Sandra and Hellman, Lars (2022). The Human Monocyte-A Circulating Sensor of Infection and a Potent and Rapid Inducer of Inflammation. International Journal of Molecular Sciences. 23 :7 , 3890
[Research article]

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Abstract

Monocytes were previously thought to be the precursors of all tissue macrophages but have recently been found to represent a unique population of cells, distinct from the majority of tissue macrophages. Monocytes and intestinal macrophages seem now to be the only monocyte/macrophage populations that originate primarily from adult bone marrow. To obtain a better view of the biological function of monocytes and how they differ from tissue macrophages, we have performed a quantitative analysis of its transcriptome in vivo and after in vitro stimulation with E. coli LPS. The monocytes rapidly responded to LPS by producing extremely high amounts of mRNA for the classical inflammatory cytokines, IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha, but almost undetectable amounts of other cytokines. IL-6 was upregulated 58,000 times, from almost undetectable levels at baseline to become one of the major transcripts already after a few hours of cultivation. The cells also showed very strong upregulation of a number of chemokines, primarily IL-8, Ccl2, Ccl3, Ccl3L3, Ccl20, Cxcl2, Cxcl3 and Cxcl4. IL-8 became the most highly expressed transcript in the monocytes already after four hours of in vitro culture in the presence of LPS. A high baseline level of MHC class II chains and marked upregulation of super oxide dismutase (SOD2), complement factor B, complement factor C3 and coagulation factor 3 (F3; tissue factor) at four hours of in vitro culture were also observed. This indicates a rapid protective response to high production of oxygen radicals, to increase complement activation and possibly also be an inducer of local coagulation. Overall, these findings give strong support for monocytes acting primarily as potent mobile sensors of infection and rapid activators of a strong inflammatory response.

Authors/Creators:Lara, Sandra and Akula, Srinivas and Fu, Zhirong and Olsson, Anna-Karin and Kleinau, Sandra and Hellman, Lars
Title:The Human Monocyte-A Circulating Sensor of Infection and a Potent and Rapid Inducer of Inflammation
Series Name/Journal:International Journal of Molecular Sciences
Year of publishing :2022
Volume:23
Number:7
Article number:3890
Number of Pages:13
Publisher:MDPI
ISSN:1661-6596
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Cell and Molecular Biology
Keywords:monocyte, macrophage, cytokine, chemokine, cytokine storm, LPS, inflammatory response, antigen presentation, G-CSF, IL-6
URN:NBN:urn:nbn:se:slu:epsilon-p-116927
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-116927
Additional ID:
Type of IDID
DOI10.3390/ijms23073890
Web of Science (WoS)000783148700001
ID Code:27725
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Anatomy, Physiology and Biochemistry
Deposited By: SLUpub Connector
Deposited On:06 May 2022 12:03
Metadata Last Modified:06 May 2022 12:11

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