Multiphoton imaging reveals a novel leukocyte recruitment paradigm in the inflamed glomerulus

Abstract

In contrast to many capillary beds, the glomerulus supports leukocyte recruitment during inflammation. However, the behaviour of leukocytes after their recruitment to the glomerulus is unknown. In this study, we used multiphoton microscopy to examine leukocyte behaviour in the glomerular microvasculature under steady‐state and inflamed conditions. In uninflamed glomeruli, neutrophils and monocytes were retained within capillaries for several minutes, during which time leukocytes were either static or migrated. Inflammation increased the duration of leukocyte retention, an effect that was eliminated via inhibition of Mac‐1. In addition, both static and migratory neutrophils generated oxidants in inflamed glomeruli. This work establishes a new paradigm for glomerular inflammation, showing that acute inflammation does not induce leukocyte recruitment per se, instead increasing the duration of leukocyte retention in the glomerulus, during which time leukocytes adopt either static or migratory behaviors. These findings describe a novel form of multicellular intravascular patrolling that may contribute to the susceptibility of the glomerulus to inflammation. Supported by the NHMRC (Australia)