Researchers at the BC Cancer Agency are investigating the activity of a protein they discovered in 1996 which regulates how we respond to microbial infections and inflammation-inducing agents. As described in a paper just published in the prestigious journal, Immunity, lead author Dr. Laura Sly has found that this protein – called SHIP (for Src homology 2-containing inositol 5'-phosphatase) – ensures that the body's macrophages and mast cells do not overreact to inflammation-inducing conditions.

This research, explains BC Cancer Agency senior scientist Dr. Gerald Krystal (the senior author on the paper) has important implications not only for cancer control, but increases our understanding of allergies and auto-immune disorders such as asthma, and could play an important role in controlling septic shock in hospital patients.

Infections occur when bacteria and other microorganisms (eg viruses) are able to enter the body by breaching the skin or linings of the gut, lungs or bladder. The body has two immune systems to help fight the invaders: the ancient innate immune system and the more recently evolved acquired (adaptive) immune system. The innate immune system is the first to respond by kicking into action the infection-fighting mast cells and macrophages which then release inflammatory cytokines and nitric oxide (NO). This causes capillaries to dilate and plasma to leak out of the bloodstream, shutting down the infected area through swelling, and thus preventing the infection from moving any further into the body.

For all its benefits, the immune system must maintain a fine balance in the body. If there is not a strong enough reaction against an invading microorganism, the microorganism can grow and spread. On the other hand, if the immune system overreacts, it can cause septic shock – a problem whose outcome costs the medical system billions of dollars each year.

Septic shock occurs when the loss of plasma from the bloodstream doesn't slow down. As a person's blood pressure drops due to this loss, not enough oxygen reaches the tissues of the body, and they begin to die. SHIP has been found to play an important role in preventing the immune system from overreacting and allowing this to happen. SHIP restricts the amount of inflammatory cytokines and NO released by the activated mast cells and macrophages living just below the surface of the skin and other linings, thus preventing septic shock.

As a result of this research, Dr. Krystal, together with Drs Alice Mui, Ray Andersen and Chris Ong, has formed a company AquaGenyx to identify small molecule activators and inhibitors of SHIP. These small molecules could prove to be very useful for treating not only septic shock, but a variety of autoimmune disorders and cancers.

Researchers are becoming more aware of the links between chronic inflammation and diseases such as gastric cancer, as well as the role of infectious microorganisms and our inflammatory response determines the fate of these and other cancers may help irradicate  them in the future.

The BC Cancer Agency, a part of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer.  It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care.  The BC Cancer Research Centre conducts research into the causes and cures for cancer. The BC Cancer Foundation supports research and care at the BC Cancer Agency.

For more information or to arrange an interview, please contact:

Nicole Adams

Public Relations Officer

BC Cancer Agency

604.877.6272

nadams@bccancer.bc.ca