The proangiogenic capacity of polymorphonuclear neutrophils delineated by microarray technique and by measurement of neovascularization in wounded skin of CD18-deficient mice
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vor 18 Jahren
Growing evidence supports the concept that polymorphonuclear
neutrophils (PMN) are critically involved in inflammation-mediated
angiogenesis which is important for wound healing and repair. We
employed an oligonucleotide microarray technique to gain further
insight into the molecular mechanisms underlying the proangiogenic
potential of human PMN. In addition to 18 known
angiogenesis-relevant genes, we detected the expression of 10 novel
genes, namely midkine, erb-B2, ets-1, transforming growth factor
receptor-beta(2) and -beta(3), thrombospondin, tissue inhibitor of
metalloproteinase 2, ephrin A2, ephrin B2 and restin in human PMN
freshly isolated from the circulation. Gene expression was confi
rmed by the RT-PCR technique. In vivo evidence for the role of PMN
in neovascularization was provided by studying neovascularization
in a skin model of wound healing using CD18-deficient mice which
lack PMN infi ltration to sites of lesion. In CD18-deficient
animals, neo- vascularization was found to be signifi cantly
compromised when compared with wild- type control animals which
showed profound neovascularization within the granulation tissue
during the wound healing process. Thus, PMN infiltration seems to
facilitate inflammation mediated angiogenesis which may be a
consequence of the broad spectrum of proangiogenic factors
expressed by these cells. Copyright (c) 2006 S. Karger AG, Basel.
neutrophils (PMN) are critically involved in inflammation-mediated
angiogenesis which is important for wound healing and repair. We
employed an oligonucleotide microarray technique to gain further
insight into the molecular mechanisms underlying the proangiogenic
potential of human PMN. In addition to 18 known
angiogenesis-relevant genes, we detected the expression of 10 novel
genes, namely midkine, erb-B2, ets-1, transforming growth factor
receptor-beta(2) and -beta(3), thrombospondin, tissue inhibitor of
metalloproteinase 2, ephrin A2, ephrin B2 and restin in human PMN
freshly isolated from the circulation. Gene expression was confi
rmed by the RT-PCR technique. In vivo evidence for the role of PMN
in neovascularization was provided by studying neovascularization
in a skin model of wound healing using CD18-deficient mice which
lack PMN infi ltration to sites of lesion. In CD18-deficient
animals, neo- vascularization was found to be signifi cantly
compromised when compared with wild- type control animals which
showed profound neovascularization within the granulation tissue
during the wound healing process. Thus, PMN infiltration seems to
facilitate inflammation mediated angiogenesis which may be a
consequence of the broad spectrum of proangiogenic factors
expressed by these cells. Copyright (c) 2006 S. Karger AG, Basel.
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