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2006 ; 10
(3
): 708-15
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A subpopulation of peritoneal macrophages form capillarylike lumens and branching
patterns in vitro
#MMPMID16989730
Anghelina M
; Moldovan L
; Zabuawala T
; Ostrowski MC
; Moldovan NI
J Cell Mol Med
2006[Jul]; 10
(3
): 708-15
PMID16989730
show ga
OBJECTIVE: We have previously shown that monocytes/macrophages (MC/Mph) influence
neovascularization by extracellular matrix degradation, and by direct
incorporation into growing microvessels. To date, neither the phenotype of these
cells, nor the stages of their capillary-like conversion were sufficiently
characterized. METHODS: We isolated mouse peritoneal Mph from transgenic mice
expressing fluorescent proteins either ubiquitously, or specifically in the
myelocytic lineage. These Mph were embedded in Matrigel which contained
fluorescent protease substrates, exposed to an MCP-1 chemotactic gradient, and
then examined by confocal microscopy after various intervals. RESULTS: Within 3
hrs after gel embedding, we detected TIMP-1 and MMP-12 dependent proteolysis of
the matrix surrounding Mph, mostly in the direction of high concentrations of
MCP-1. After 2 days, Mph developed intracellular vacuoles containing degradation
product. At 5 days these vacuoles were enlarged and/or fused to generate
trans-cellular lumens in approximately 10% of cells or more (depending on
animal's genetic background). At this stage, Mph became tubular, and occasionally
organized in three-dimensional structures resembling branched microvessels.
CONCLUSION: Isolated mouse peritoneal Mph penetrate Matrigel and form tunnels via
a metalloprotease-driven proteolysis and phagocytosis. Following a morphological
adjustment driven by occurrence, enlargement and/or fusion process of
intracellular vacuoles, similar to that described in bona fide endothelium, a
subpopulation of these cells end up by lining a capillary-like lumen in vitro.
Thus we show that adult Mph, not only the more primitive 'endothelial
progenitors', have functional properties until now considered defining of the
endothelial phenotype.