In the migration of neutrophils from blood vessels into the tissues, the first step is binding of the neutrophils to the endothelium of the blood vessels (marginalization).

Marginalization is due to certain molecules, called cell adhesion molecules (CAMs), found on the surfaces of neutrophils and on endothelial cells.

The binding of adhesion molecules occurs in two steps. In the first step, adhesion molecules called selectins lightly tether the neutrophil to the endothelium, so that it begins rolling along the surface, in a second step, a much tighter binding occurs through the interaction of CAMs on the endothelial cells with integrins on the neutrophils.

Once outside the blood vessel, a neutrophil is guided towards an infection by various diffusing chemotactic factors. Examples include the chemokines and the complement peptide C5a that is released when the complement system is activated either via specific immunity or innate immunity.