White blood cells play a vital role in human health by responding to injury or infection. But occasionally these defensive cells can become too much of a good thing.
Oklahoma Medical Research Foundation scientist Rodger McEver, M.D., has discovered that blocking a specific cell interaction can prevent white blood cell-induced damage during inflammation. The research was published in the Journal of Experimental Medicine.
The recruitment of neutrophils — a type of rapid-attack white blood cell — is essential in the process of fighting injuries and infections. However, excessive accumulation of neutrophils can cause inflammation-based injuries, contributing to stroke, heart attack, dysfunction in transplanted organs and deep-vein thrombosis.
McEver’s lab studies the process of inflammation, where white blood cells rush into the tissues to fight off invaders or assist in injury healing.
“Neutrophils come in the first wave of inflammation,” said McEver, chair of OMRF’s Cardiovascular Biology Research Program. “Those cells act like military: they’re armed and patrolling the blood. They are designed for good but can be quite destructive, so you obviously want that force used in a positive way.”
In the process of responding, circulating neutrophils attach to blood vessel surfaces at sites of injury or infection in the tissues. Molecules called selectins enable the circulating white blood cells to roll along the vessel surface. Other molecules called integrins then tell the rolling cells when to stop so they can penetrate the vessel wall into the tissue.
McEver and his lab have discovered that there are actually two actions that allow integrins to function. The discovery builds on previous research conducted by McEver and scientists at OMRF.
“We have learned that extending the integrin alone is not enough to complete the process,” said McEver, who holds the Alvin Chang Chair in Cardiovascular Biology. “The integrin has to open up again to really grab hold of its counterpart on the blood vessel surface for the white blood cells to come to a halt. Then they can enter the tissues and do their job. That’s a good thing.”
If the recruitment of these cells is not regulated properly, too many come to the tissue and can contribute to disease. If the numbers are too few, they cannot effectively fight the infection or disease.
McEver said blocking this second action can defend against over-recruitment of white blood cells to a specific area where they can cause harm.
“Inflammation is good most of the time, but it’s always a two-edged sword,” said McEver. “White blood cells arriving in just the right numbers and in just the right location is pivotal. These new findings help us understand the process even more.”
The research was funded in part by National Institutes of Health grant No. HL034363 through the National Heart, Lung, and Blood Institute.