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Comparative Study
. 2009 Aug;29(8):1193-9.
doi: 10.1161/ATVBAHA.109.187450. Epub 2009 Jun 4.

Monocytes and neutrophils exhibit both distinct and common mechanisms in penetrating the vascular basement membrane in vivo

Mathieu-Benoît Voisin  1 , Abigail Woodfin, Sussan Nourshargh
Affiliations
Comparative Study

Monocytes and neutrophils exhibit both distinct and common mechanisms in penetrating the vascular basement membrane in vivo

Mathieu-Benoît Voisin et al. Arterioscler Thromb Vasc Biol. 2009 Aug.

Abstract

Objective: 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.

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Figures

Figure 1
Figure 1
CCL2-induced monocyte and neutrophil transmigration through LERs and BM remodeling. A, Images of control and CCL2-stimulated cremasteric venules. B, Time course of monocyte and neutrophils transmigration. C, Venular cross-sections with leukocytes migrating through Lmα5 LERs. D, Time course of the remodeling of the LER area. (Please see the supplemental materials for details).
Figure 2
Figure 2
CCL2-induced neutrophil-dependent LER remodeling. A, Effect of neutrophil depletion on leukocyte transmigration response and Lmα5 LERs remodeling. B, Percentage of transmigrating monocytes associated with a BM LER. (Please see the supplemental materials for details).
Figure 3
Figure 3
Monocyte protrusion formation while penetrating LERs. A, Monocytes embedded within the BM and exhibiting at least 3 distinct morphological shapes after CCL2-stimulation. B, Venular cross-section showing a monocyte squeezing both its body and nucleus. C, Schematic diagram of the different stages of monocyte migration. (Please see the supplemental materials for details).
Figure 4
Figure 4
Neutrophil protrusion formation during venular BM penetration. A, Morphology of 2 neutrophils migrating through the BM after CCL2 stimulation. B and C, Neutrophil and monocyte infiltration and their morphology during transmigration through the BM after LTB4 (B) or LPS (C) stimulation. D, Diameter of “invasive” protrusions. (Please see the supplemental materials for details).
Figure 5
Figure 5
Neutrophil but not monocyte transmigration is associated with the carriage of Lmα5 on the emigrated cells (A), and both neutrophil migration and LER remodeling are suppressed by a neutrophil elastase inhibitor (B). C, Schematic diagram of the different stages of monocyte and neutrophil migration. (Please see the supplemental materials for details).
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