title: Group X secretory PLA2 in neutrophils plays a pathogenic role in abdominal aortic aneurysms in mice.
abstract: Group X secretory PLA(2) (sPLA(2)-X) is expressed in neutrophils and plays a role in the pathogenesis of neutrophil-mediated tissue inflammation and injury. This study tested the hypothesis that sPLA(2)-X in neutrophils may contribute to the pathogenesis of abdominal aortic aneurysms (AAA) using sPLA(2)-X(-/-) mice. AAA was created by application of CaCl(2) to external surface of aorta. As a result, the aortas of sPLA(2)-X(-/-) mice had smaller diameters (percent increase from baseline; 24.8 ± 3.5% vs. 49.9 ± 9.1%, respectively; P < 0.01), a reduced grade of elastin degradation, and lower activities of elastase and gelatinase (26% and 19% lower, respectively) after CaCl(2) treatment compared with sPLA(2)-X(+/+) mice. In sPLA(2)-X(+/+) mice, immunofluorescence microscopic images showed that the immunoreactivity of sPLA(2)-X was detected only in neutrophils within aortic walls 3 days, 1, 2, and 6 wk after CaCl(2) treatment, whereas the immunoreactivity was not detected in macrophages or mast cells in aortic walls. sPLA(2)-X immunoreactivity also was colocalized in cells expressing matrix metalloproteinase (MMP)-9. Neutrophils isolated from sPLA(2)-X(-/-) mice had lower activities of elastase, gelatinase, and MMP-9 in response to stimuli compared with sPLA(2)-X(+/+) mice. The attenuated release of elastase and gelatinase from sPLA(2)-X(-/-) neutrophils was reversed by exogenous addition of mouse sPLA(2)-X protein. The adoptive transfer of sPLA(2)-X(+/+) neutrophils days 0 and 3 after CaCl(2) treatment reversed aortic diameters and elastin degradation grades in the lethally irradiated sPLA(2)-X(+/+) mice reconstituted with sPLA(2)-X(-/-) bone marrow to an extent similar to that seen in sPLA(2)-X(+/+) mice. In conclusion, sPLA(2)-X in neutrophils plays a pathogenic role in AAA in a mice model.
authors: Department of Internal Medicine II, University of Yamanashi, Chuo, Japan.
authors: Kazuhiro
authors: K
authors: Watanabe
authors: Daisuke
authors: D
authors: Fujioka
authors: Yukio
authors: Y
authors: Saito
authors: Takamitsu
authors: T
authors: Nakamura
authors: Jun-ei
authors: JE
authors: Obata
authors: Kenichi
authors: K
authors: Kawabata
authors: Yosuke
authors: Y
authors: Watanabe
authors: Hideto
authors: H
authors: Mishina
authors: Shun
authors: S
authors: Tamaru
authors: Kohji
authors: K
authors: Hanasaki
authors: Kiyotaka
authors: K
authors: Kugiyama
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001011:Aorta / Q000201:enzymology* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016026:Bone Marrow Transplantation; D002122:Calcium Chloride; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D054509:Group X Phospholipases A2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000201:enzymology* / Q000637:transplantation; D010196:Pancreatic Elastase / Q000378:metabolism; D013997:Time Factors
chemical_list: D004549:Elastin; D054509:Group X Phospholipases A2; C516366:Pla2g10 protein, mouse; D010196:Pancreatic Elastase; D018093:Gelatinases; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D002122:Calcium Chloride