Alberta Innovates- Health Solutions

Daniel is 14 years old and loves sports. He's cut out competitive swimming though, because diving into cool water makes him wheeze.

Taking part in track and field sports brings on coughing spells that make him tired and listless. He feels lucky because his main passion, hockey, doesn't bring on breathing problems. Daniel has asthma, an incurable yet manageable disease that is estimated to affect 10-15% of all Canadian school children in varying degrees of severity.

Asthma is triggered by a number of factors: allergies, drying of lung passages due to increased breathing during exercise, even emotions, although it is not a psychological disease. During an asthma attack, the air passages in the lungs, the bronchial tubes, become inflamed and swollen, reducing breathing ability. Mucus can clog some of the airways, further hampering air exchange and trapping stale air in the lungs. When breathing gets difficult, asthmatics like Daniel often use an inhaler that sprays drugs into the lungs to dilate them and allows increased air exchange.

Asthma is one of the many conditions that can result when the body's inflammation response goes haywire. Heritage researcher Dr. Kamala Patel, a recent arrival to the University of Calgary, studies the mechanics of the human immune system during states of normal and abnormal inflammation.

A normal inflammatory response means the body's defense system is busy fighting off a foreign invader - a virus, bacteria, or parasite. Various types of white blood cells, also known as leukocytes, make up the defense system, and they patrol through the bloodstream. When the body has to defend itself from foreign invasion, or when an inflammatory reaction occurs, the leukocytes move from the bloodstream into the affected tissue.

Dr. Patel has videotaped the multi-step, acrobatic process leukocytes go through in order to get from the bloodstream to the injury. "First, they begin by tethering, just barely grabbing onto adhesion proteins imbedded in the vessel lining. The leukocytes then roll, one over another, along the blood vessel, until endothelial cell signals tell them to stop at the site where they are needed. Still following signals, the leukocytes crawl to cell junctions and push in between cells to get to the site of injury where they can do their job."

When leukocytes "overdo" their job, disease can result. Uncontrolled inflammation can lead to such conditions as inflammatory bowel disease, damage to the heart after heart stoppage, and asthma. Dr. Patel's current research focus is eosinophils, a type of leukocyte implicated in asthma.

Eosinophils are granulocytes, so named because they contain protein granules that are toxic to parasites and very destructive to tissue. Often, if blood tests show an elevation of eosinophils, which normally occur in the body in very small amounts of around 1 - 4% of all leukocytes, it can indicate the presence of parasites. Eosinophils are also present at higher than normal levels in people with certain skin allergies and in asthmatics, who often have allergies. For reasons that scientists are trying to determine, asthma can trigger production of eosinophils which then attack the tissue of the lung lining, in an inflammatory overreaction.

Dr. Patel's research centres on identifying the signals that recruit eosinophils from the bloodstream through blood vessel walls and into tissue. In a disease state such as asthma, stimuli might be producing increased numbers of adhesion proteins that are selective for eosinophils. Alternatively, the type of eosinophils in asthmatics might be different from those in non-asthmatics.

To test these ideas, she has set up a flow chamber in her lab that simulates the blood rushing through blood vessels. Endothelial cells isolated from discarded human umbilical cords are placed in the flow chamber and stimulated with substances implicated in allergic disease. This tissue culture system allows Dr. Patel to follow several lines of inquiry about eosinophil function. "What adhesion proteins grab eosinophils from the bloodstream? What signal transduction events then occur inside the eosinophil? How do these cells get between cell junctions? That's the type of information that's known for white blood cells like neutrophils and lymphocytes, which have been closely studied and have been the target of new therapeutics to treat disease. But the mechanics of eosinophil function are still largely unknown although research in this area has increased dramatically over the last five years." University of Alberta Heritage Senior Scholar Dr. Redwan Moqbel is also contributing significantly to research on eosinophils.

Some of what is known is that eosinophils make cytokines, the messengers of the immune system. Different cytokines recruit different types of leukocytes to perform a range of functions from wound healing and tissue remodelling, to tissue destruction. If Dr. Patel can decode how eosinophils move from the bloodstream to tissue, it could be the first step toward modulating their function in inflammatory reactions such as asthma and some types of allergies.

Dr. Kamala Patel is a Heritage Scholar at the University of Calgary and a 1997-98 recipient of the Calgary Herald Award.

For related websites please check: