Monocytes and Neutrophils Exhibit Both Distinct and Common Mechanisms in Penetrating the Vascular Basement Membrane In Vivo

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Abstract
Objectives— Leukocyte migration through venular walls is a fundamental event during inflammation, but many aspects of this response, including the mechanisms associated with leukocyte migration through the vascular basement membrane (BM) in vivo, are poorly understood. Here we investigated and compared the means by which neutrophils and monocytes migrate through the venular BM. Specifically, as we have previously reported on the existence of neutrophil permissive sites (termed matrix protein low expression regions; LERs) within the venular BM, we have now investigated the role of these sites in monocyte transmigration in vivo. Methods and Results— Analysis of CCL2-stimulated mouse cremaster muscles by immunofluorescent staining and confocal microscopy demonstrated that both neutrophils and monocytes use LERs for penetrating venular walls, but independent and distinct mechanisms are used by the 2 cell types. Collectively, (1) neutrophil but not monocyte transmigration led to enlargement of LERs, (2) monocytes showed a greater extent of deformability in migrating through the venular BM, and (3) only extravasated neutrophils were associated with the carriage of laminin fragments. Conclusions— The findings provide novel insights into mechanisms of leukocyte transmigration by presenting the first in vivo evidence for distinct modes used by neutrophils and monocytes in penetrating the vascular BM.