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Göteborgs universitets publikationer

The absence of platelet-derived growth factor-B in circulating cells promotes immune and inflammatory responses in atherosclerosis-prone ApoE-/- mice.

Författare och institution:
Jingjing Tang (-); Koichi Kozaki (-); Andrew G Farr (-); Paul J Martin (-); Per Lindahl (Institutionen för medicinsk och fysiologisk kemi); Christer Betsholtz (Institutionen för medicinsk och fysiologisk kemi); Elaine W Raines (-)
Publicerad i:
The American journal of pathology, 167 ( 3 ) s. 901-12
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Both innate and adaptive immunity contribute to the progression of inflammatory-fibrotic lesions of atherosclerosis. Although platelet-derived growth factor (PDGF)-B has been investigated as a stimulant of smooth muscle cells in vascular diseases, its effects on the immune response during disease have not been evaluated in vivo. We used hematopoietic chimeras generated after lethal irradiation of ApoE-/- recipients to test the role of PDGF in atherosclerosis. Monocyte accumulation in early atherosclerotic lesions increased 1.9-fold in ApoE-/-/PDGF-B-/- chimeras. Lymphocytes from null chimeras showed a 1.6- to 2.0-fold increase in the number of activated CD4(+) T cells and a 2.5-fold elevation of interferon-gamma-secreting CD4(+) T cells on ex vivo challenge with modified low-density lipoprotein. Splenocyte transcript levels were also altered with a twofold decrease in interleukin-10 and 1.7- and 3.0-fold increases in interleukin-18 and CCR 5, respectively. These cellular and molecular changes were consistent with a shift to a proinflammatory phenotype in null chimeras. Our data also demonstrated for the first time the presence of a recently discovered family of negative regulators of innate and adaptive immunity, the suppressors of cytokine signaling (SOCS), in developing atherosclerotic lesions. Thus, our studies identify two independent negative immune regulatory pathways-PDGF-B and SOCS-that may help limit lesion expansion.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Animals, Apolipoproteins E, deficiency, genetics, Arteriosclerosis, complications, genetics, immunology, pathology, Blood Cells, metabolism, Bone Marrow Cells, metabolism, Carrier Proteins, metabolism, Chimera, Gene Expression Profiling, Genetic Predisposition to Disease, Inflammation, etiology, Ligands, Lymphocyte Activation, Macrophages, metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Monocytes, pathology, Platelet-Derived Growth Factor, metabolism, Proto-Oncogene Proteins c-sis, deficiency, genetics, RNA, Messenger, metabolism, Receptor, Platelet-Derived Growth Factor alpha, genetics, Repressor Proteins, metabolism, Suppressor of Cytokine Signaling Proteins, T-Lymphocytes, immunology, Transcription Factors, metabolism
Postens nummer:
Posten skapad:
2007-11-12 11:51
Posten ändrad:
2011-01-20 09:59

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