Neutrophil transmigration: emergence of an adhesive cascade within venular walls

Recruitment of neutrophils from the blood circulation to sites of infection or injury is a key innate immune response against invading pathogens and tissue injury. However, if inappropriately triggered, excessive and/or prolonged, this host defence response can also lead to severe pathological disorders. The migration of all leucocytes out of the vasculature is classically described by the leucocyte adhesion cascade that depicts a well-characterised sequence of cellular and molecular events within the vascular lumen. Recent findings have now illustrated that beyond the vascular lumen, the breaching of the venular wall can also involve an analogous cascade of adhesive events. For neutrophils this involves a tightly regulated and sequential series of responses within venular walls, initiating with adhesive steps that guide neutrophils through endothelial cells lining the venular wall, followed by responses that mediate and regulate their migration through the pericyte sheath and the venular basement membrane. The present review aims to provide a brief summary of novel additions to the classical adhesion cascade within the vascular lumen and then to discuss the emergence of a second adhesion cascade for neutrophils within venular walls, the latter illustrating the intricacies and complexities of neutrophil transmigration.