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Defective angiogenesis in the inflammatory granulation tissue in histidine decarboxylase-deficient mice but not in mast cell-deficient mice.

Ghosh AK, Hirasawa N, Ohtsu H, Watanabe T, Ohuchi K - J. Exp. Med. (2002)

Bottom Line: The topical injection of histamine or the H(2) agonist dimaprit rescued the defective angiogenesis and granulation tissue formation in HDC(-/-) mice.In addition, macrophages in the granulation tissue were found to express HDC.Our findings indicate that histamine derived from non-mast cells plays a significant role in the angiogenesis of the inflammatory granulation tissue.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi 980-8578, Japan.

ABSTRACT
We have analyzed the role of histamine in the angiogenesis of the granulation tissue in histidine decarboxylase-deficient (HDC(-/-)) mice, mast cell-deficient mice (WBB6F1-W/W(V)), and their corresponding wild-type mice (HDC(+/+) and WBB6F(1)(+/+)). In HDC(+/+) mice, subcutaneous implantation of a cotton thread in the dorsum induced granulation tissue formation with angiogenesis, while the topical injection of anti-vascular endothelial growth factor (VEGF) IgG strongly suppressed them. In HDC(-/-) mice which showed lower VEGF levels in the granulation tissue, there was notably less angiogenesis and granulation tissue formation than in HDC(+/+) mice. The topical injection of histamine or the H(2) agonist dimaprit rescued the defective angiogenesis and granulation tissue formation in HDC(-/-) mice. There was no significant difference in the granulation tissue formation and angiogenesis between WBB6F1-W/W(V) and WBB6F1(+/+) mice. In addition, macrophages in the granulation tissue were found to express HDC. Our findings indicate that histamine derived from non-mast cells plays a significant role in the angiogenesis of the inflammatory granulation tissue.

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Immunohistochemical observation for CD31 expression in the granulation tissue in mice. A cotton thread (1 cm, 7 mg) was implanted subcutaneously in the dorsum of each mouse. The mice were killed 5 d after cotton thread implantation. The sections of the granulation tissue were immunostained using an antibody to CD31, a marker for endothelial cells. CD31 expression in the granulation tissue in HDC+/+ mice (A) and in HDC−/− mice (B) was observed with a light microscope (original magnification: ×200). Representative micrographs are shown from three samples.
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fig4: Immunohistochemical observation for CD31 expression in the granulation tissue in mice. A cotton thread (1 cm, 7 mg) was implanted subcutaneously in the dorsum of each mouse. The mice were killed 5 d after cotton thread implantation. The sections of the granulation tissue were immunostained using an antibody to CD31, a marker for endothelial cells. CD31 expression in the granulation tissue in HDC+/+ mice (A) and in HDC−/− mice (B) was observed with a light microscope (original magnification: ×200). Representative micrographs are shown from three samples.

Mentions: To clarify the role of histamine in angiogenesis, we implanted a cotton thread in the dorsum of HDC−/− mice. Vascular network formation in the granulation tissue and the subcutaneous tissue beneath the cotton thread in HDC−/− mice 3 and 5 d after cotton thread implantation was notably less than those in HDC+/+ mice (Fig. 3 A). In addition, the granulation tissue formation (Fig. 3 B), as well as the levels of hemoglobin (Fig. 3 C) and VEGF protein in the granulation tissue (Fig. 3 D) of HDC−/− mice were significantly less than those in HDC+/+ mice 3 and 5 d after cotton thread implantation. Concentrations of VEGF proteins in the supernatant of the homogenate of the cotton thread induced-granulation tissue determined by ELISA also revealed that the levels of VEGF proteins in the granulation tissue 3 to 7 d after cotton thread implantation were lower in HDC−/− mice than in HDC+/+ mice (Table I). In addition, immunohistochemical analysis of the granulation tissue dissected 5 d after the cotton thread implantation using an antibody to CD31, a marker for endothelial cells, indicated that the neovascular density in the granulation tissue in HDC−/− mice was obviously less than that in HDC+/+ mice (Fig. 4) . These findings indicate that histamine plays an important role in the induction of VEGF and angiogenesis during the early stage of cotton thread-induced granulation tissue.


Defective angiogenesis in the inflammatory granulation tissue in histidine decarboxylase-deficient mice but not in mast cell-deficient mice.

Ghosh AK, Hirasawa N, Ohtsu H, Watanabe T, Ohuchi K - J. Exp. Med. (2002)

Immunohistochemical observation for CD31 expression in the granulation tissue in mice. A cotton thread (1 cm, 7 mg) was implanted subcutaneously in the dorsum of each mouse. The mice were killed 5 d after cotton thread implantation. The sections of the granulation tissue were immunostained using an antibody to CD31, a marker for endothelial cells. CD31 expression in the granulation tissue in HDC+/+ mice (A) and in HDC−/− mice (B) was observed with a light microscope (original magnification: ×200). Representative micrographs are shown from three samples.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193691&req=5

fig4: Immunohistochemical observation for CD31 expression in the granulation tissue in mice. A cotton thread (1 cm, 7 mg) was implanted subcutaneously in the dorsum of each mouse. The mice were killed 5 d after cotton thread implantation. The sections of the granulation tissue were immunostained using an antibody to CD31, a marker for endothelial cells. CD31 expression in the granulation tissue in HDC+/+ mice (A) and in HDC−/− mice (B) was observed with a light microscope (original magnification: ×200). Representative micrographs are shown from three samples.
Mentions: To clarify the role of histamine in angiogenesis, we implanted a cotton thread in the dorsum of HDC−/− mice. Vascular network formation in the granulation tissue and the subcutaneous tissue beneath the cotton thread in HDC−/− mice 3 and 5 d after cotton thread implantation was notably less than those in HDC+/+ mice (Fig. 3 A). In addition, the granulation tissue formation (Fig. 3 B), as well as the levels of hemoglobin (Fig. 3 C) and VEGF protein in the granulation tissue (Fig. 3 D) of HDC−/− mice were significantly less than those in HDC+/+ mice 3 and 5 d after cotton thread implantation. Concentrations of VEGF proteins in the supernatant of the homogenate of the cotton thread induced-granulation tissue determined by ELISA also revealed that the levels of VEGF proteins in the granulation tissue 3 to 7 d after cotton thread implantation were lower in HDC−/− mice than in HDC+/+ mice (Table I). In addition, immunohistochemical analysis of the granulation tissue dissected 5 d after the cotton thread implantation using an antibody to CD31, a marker for endothelial cells, indicated that the neovascular density in the granulation tissue in HDC−/− mice was obviously less than that in HDC+/+ mice (Fig. 4) . These findings indicate that histamine plays an important role in the induction of VEGF and angiogenesis during the early stage of cotton thread-induced granulation tissue.

Bottom Line: The topical injection of histamine or the H(2) agonist dimaprit rescued the defective angiogenesis and granulation tissue formation in HDC(-/-) mice.In addition, macrophages in the granulation tissue were found to express HDC.Our findings indicate that histamine derived from non-mast cells plays a significant role in the angiogenesis of the inflammatory granulation tissue.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi 980-8578, Japan.

ABSTRACT
We have analyzed the role of histamine in the angiogenesis of the granulation tissue in histidine decarboxylase-deficient (HDC(-/-)) mice, mast cell-deficient mice (WBB6F1-W/W(V)), and their corresponding wild-type mice (HDC(+/+) and WBB6F(1)(+/+)). In HDC(+/+) mice, subcutaneous implantation of a cotton thread in the dorsum induced granulation tissue formation with angiogenesis, while the topical injection of anti-vascular endothelial growth factor (VEGF) IgG strongly suppressed them. In HDC(-/-) mice which showed lower VEGF levels in the granulation tissue, there was notably less angiogenesis and granulation tissue formation than in HDC(+/+) mice. The topical injection of histamine or the H(2) agonist dimaprit rescued the defective angiogenesis and granulation tissue formation in HDC(-/-) mice. There was no significant difference in the granulation tissue formation and angiogenesis between WBB6F1-W/W(V) and WBB6F1(+/+) mice. In addition, macrophages in the granulation tissue were found to express HDC. Our findings indicate that histamine derived from non-mast cells plays a significant role in the angiogenesis of the inflammatory granulation tissue.

Show MeSH
Related in: MedlinePlus