Four amino acids tune neutrophil adhesion in lab study

At the wall of a blood vessel, a neutrophil must first slow down, grip the vessel and then move into surrounding tissue. A University of Liverpool study found that adding four amino acids to kindlin-3 can strengthen that grip by making the protein more effective at the cell membrane.

Kindlin-3 is produced by the FERMT3 gene and helps activate integrins, the adhesion proteins that let neutrophils attach firmly to blood vessels. The researchers found that alternative splicing — a process that lets one gene produce slightly different versions of a protein — creates a longer form of kindlin-3. That form was previously considered nonfunctional, but the study found it improves integrin activation and neutrophil adhesion.

The longer protein appeared more often during stress myelopoiesis, the rapid production and mobilization of blood cells in response to infection, inflammation or recovery after stem cell transplantation. Madeleine Vidal, an integrated master's student at Liverpool and joint first author, carried out key biochemical experiments. Professor Benjamin Goult was a co-corresponding author.

The mechanism may help researchers understand immune recovery after stem cell transplantation, a potentially lifesaving treatment for blood cancers and other serious blood disorders. Around 4,000 stem cell transplants are carried out in the UK each year. It also adds detail to leukocyte adhesion deficiency type III, or LAD-III, a rare inherited condition in which immune cells cannot adhere normally and patients can suffer recurrent infections.

Concretely, the finding changes the biological explanation rather than patient care today: it identifies a specific protein form that researchers can examine during immune recovery and in LAD-III. The study offers no treatment or clinical deployment date, but it shows how a molecular adjustment as small as four amino acids can tune the behavior of an immune cell when demand rises.