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Role of Complement Inhibitor Factor H in Monocyte differentiation

Mueni, Christine Mercy (2019) MOBN03 20182
Degree Projects in Molecular Biology
Popular Abstract
Complement inhibitors in cancer - supporting the enemy

Cancer is one of the leading causes of deaths worldwide. In 2018 alone, 9.6 million deaths were due to cancer. Cancer cells themselves and the sites they colonize play an important role in cancer growth, progression and response to treatment. There are many factors that exist in body areas affected by cancer including components of the immune system. Innate immune system is the primary guard against infections, tissue injury as well as cancer. This system is made up of different cells with main function of eating (phagocytosis) invading disease causing agents, damaged and cancer cells. Another mechanism used by innate immune system to fulfil its’ role is through a group of proteins... (More)
Complement inhibitors in cancer - supporting the enemy

Cancer is one of the leading causes of deaths worldwide. In 2018 alone, 9.6 million deaths were due to cancer. Cancer cells themselves and the sites they colonize play an important role in cancer growth, progression and response to treatment. There are many factors that exist in body areas affected by cancer including components of the immune system. Innate immune system is the primary guard against infections, tissue injury as well as cancer. This system is made up of different cells with main function of eating (phagocytosis) invading disease causing agents, damaged and cancer cells. Another mechanism used by innate immune system to fulfil its’ role is through a group of proteins called complement system. When the complement proteins encounter danger signals from infectious agents, damaged or cancer cells they become activated. The activated proteins in turn release factors that bind on to the infectious agent, damaged or cancer cells enabling their phagocytosis and removal from the body. However, insufficient activation of complement proteins can lead to infections as well as cancer growth while excessive, uncontrolled activation can cause damage of the host tissues leading to diseases known as autoimmune or autoinflammatory. Some complement proteins function is to block excessive and unwanted activation of complement. These proteins are referred to as complement inhibitors. However, despite complement being one of important mechanism used by innate immune system to combat the enemy, some cancer cells secrete complement inhibitors. This in turn prevent complement activation required to clear the cancer cells thus supporting cancer existence in the body. In addition, cells of innate immune system; - the monocytes and macrophages also exist at cancer sites. This means monocytes, macrophages and complement inhibitors can be present in cancer sites at the same time.

This study aim was to investigate the effect of one of the complement inhibitors on monocytes and macrophages involved in cancer regulation. Monocytes were incubated with complement inhibitor and their functions studied. We observed that, macrophages that usually have cancer removal properties changed their appearance towards appearance of macrophages that were under influence of complement inhibitor. There was also a similarity between macrophages that prevent inflammation and macrophages that were obtained from monocytes incubated with complement inhibitor. We then hypothesized that, macrophages obtained from monocytes under influence of the inhibitor and those that prevent inflammation have a similar receptor responsible for their functions. This was investigated by incubating monocytes with agents responsible for blocking the receptor function. However, blocking the receptor function did not abolish the activity of complement inhibitors on monocytes, implying that this receptor has no role in observed monocyte-macrophage changes. Monocytes under influence of complement inhibitor were also tested on their ability to activate T cells, which are immune cells of the second arm of body defense (adaptive immune system). The resulting T cell response was however very low. This suggests that macrophages under influence of complement inhibitor that was studied are inefficient in removal of cancer cells from the body. These findings therefore imply that presence of complement inhibitors in tumors should be taken in consideration when identifying possible treatment targets in cancer.

Master’s Degree Project in Molecular Biology, Medical Biology specialization, 60 Credits, 2019
Department of Biology, Lund University.


Supervisors: Professor Anna Blom and Karolina Smolag
Department of Translational Medicine, Division of Medical Protein Chemistry, Lund University. (Less)
Please use this url to cite or link to this publication:
author
Mueni, Christine Mercy
supervisor
organization
course
MOBN03 20182
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8997185
date added to LUP
2019-10-28 11:55:52
date last changed
2019-10-28 11:55:52
@misc{8997185,
  author       = {{Mueni, Christine Mercy}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Role of Complement Inhibitor Factor H in Monocyte differentiation}},
  year         = {{2019}},
}