During the inflammatory reaction to an invading pathogen neutrophils arrive at the injury site and leave blood vessels to accumulate around foreign particles. Leukocytes exiting the bloodstream have to breach first through endothelial cells before they enter the interstitial space. The publication I am discussing today adds yet another step to this route as it analyzes how neutrophils migrate through the layer of pericytes that coats endothelial cells. Pericytes are cells that form the important structural part of certain types of blood vessels (capillaries, postcapillary venules, and collecting venules); however, their participation in leukocyte passage was previously unstudied. This paper extends the knowledge of neutrophil migration to the inflamed tissue by describing the novel type of movement coined abluminal crawling and exploring many intricacies of neutrophils/pericytes interactions. My experience in the main technique applied by authors – the real-time in vivo imaging – is next to nothing, but I can still admire how they put to use their skills.
Investigators visualize pericytes and neutrophils by generating the mouse strain that has fluorescent proteins expressed in the above cell types. Additionally, endothelial cells are made visible with the in vivo application of specific immuno-staining. The migration of neutrophils to peripheral tissue is provoked by the injection of potent inflammatory agent (TNF) into the exposed body part of such mice (cremasteric muscle located in the scrotum). Authors observe that after the rapid breach through endothelial cells neutrophils display prolonged association with the pericyte layer combined with the movement along pericyte processes – the already mentioned abluminal crawling. The abluminal crawling ends when a neutrophil leaves into the interstitial space through a gap between pericytes.
How the abluminal crawling is regulated? The efficient neutrophil movement along pericytes depends on the expression of ICAM-1 (on pericytes) as well as Mac-1 and LFA-1 (on neutrophils). The average gap size between pericytes (which is proposed by investigators to be one of decisive factors underlying successful migration) is enlarged by the injection of proinflammatory cytokines TNF and IL-1β and pericytes express receptors recognizing these mediators. Authors also show the intriguing data suggesting that the gap choice by neutrophils is apparently not random as very often a single gap is used by multiple neutrophils. To sum up, this report implicates that pericytes may participate in the immune response by influencing the neutrophil migration into periphery.
Proebstl D, Voisin MB, Woodfin A, Whiteford J, D’Acquisto F, Jones GE, Rowe D, & Nourshargh S (2012). Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. The Journal of experimental medicine, 209 (6), 1219-34 PMID: 22615129