Oxidatively modified low density lipoprotein is a chemoattractant for human T lymphocytes.

McMurray, Heather F.; Parthasarathy, S.; Steinberg, Daniel

doi:10.1172/jci116605

Cited by 245 publications

(127 citation statements)

References 30 publications

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“…Moreover, it is well known that OxLDL induces a variety of cellular responses in vascular wall cells and circulating cells. For example, OxLDL is a chemoattractant for endothelial cells and T-lymphocytes (39,40). It increases the expression of VCAM-1 and P-selectin and the release of endothelin and interleukin-8 (41)(42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

SREC-II, a New Member of the Scavenger Receptor Type F Family, Trans-interacts with SREC-I through Its Extracellular Domain

Ishii

Adachi

Aoki³

et al. 2002

Journal of Biological Chemistry

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The scavenger receptor expressed by endothelial cells (SREC) with an extremely large cytoplasmic domain, was originally identified in a human endothelial cell line. In this study, we have cloned a second isoform named SREC-II and shown that there is a heterophilic interaction between SREC-I and -II at their extracellular domains. The cDNA for murine SREC-II encodes an 834-amino acid protein with 35% homology to SREC-I. Similar to SREC-I, SREC-II contains multiple epidermal growth factor-like repeats in its extracellular domain. However, in contrast to SREC-I, SREC-II had little activity to internalize modified low density lipoproteins (LDL). A Northern blot analysis revealed a tissue expression pattern of SREC-II similar to that of SREC-I with predominant expression in human heart, lung, ovary, and placenta. Mouse fibroblast L cells with no tendency to associate showed noticeable aggregation when SREC-I was overexpressed in these cells, whereas overexpression of SREC-II caused only slight aggregation. Remarkably, intense aggregation was observed when SREC-I-expressing cells were mixed with those expressing SREC-II. Deletion of almost all of the cytoplasmic receptor domain had no effect on the receptor expression and cell aggregation, indicating that solely the extracellular domain is involved in cell aggregation. The association of SREC-I and -II was effectively suppressed by the presence of scavenger receptor ligands such as acetylated LDL and oxidized LDL. These findings suggest that SREC-I and -II show weak cell-cell interaction by their extracellular domains (termed homophilic trans-interaction) but display strong heterophilic transinteraction through the extracellular epidermal growth factor-like repeat domains.

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Section: Discussionmentioning

confidence: 99%

SREC-II, a New Member of the Scavenger Receptor Type F Family, Trans-interacts with SREC-I through Its Extracellular Domain

Ishii

Adachi

Aoki³

et al. 2002

Journal of Biological Chemistry

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“…32 Furthermore, LPC has been shown to be chemotactic for T lymphocytes and monocytes. 33,34 An interesting possibility is that antibodies to LPC/oxLDL could form immune complexes, which could be taken up by phagocytosis in the artery wall, leading to foam cell formation. In line with this, PLA 2 -modified LDL is taken up by macrophages, which develop into foam cells.…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidylcholine Is Involved in the Antigenicity of Oxidized LDL

Huang

Elinder

et al. 1998

ATVB

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Abstract-Lysophosphatidylcholine (LPC) is formed by hydrolysis of PC in low density lipoprotein (LDL) and cell membranes by phospholipase A 2 or by oxidation. Oxidized (ox) LDL activates endothelial cells, an effect mimicked by LPC. oxLDL also has the capacity to activate T and B cells, and antibody titers to oxLDL are related to the degree of atherosclerosis. The antigen in oxLDL responsible for its immune-stimulatory capacity is not well characterized, and we hypothesized that LPC was involved. We demonstrate herein the presence of antibodies against LPC, both of the IgG and IgM isotype, in 210 healthy individuals. This antibody reactivity was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only palmitic acid showed antibody titers equivalent to those of LPC containing unsaturated fatty acids. Antibody titers to PC were low compared with LPC, and hydrolysis of PC at the sn-2 position is thus essential for immune reactivity. There was a close correlation between anti-oxLDL and anti-LPC antibodies. Furthermore, LPC competitively inhibited anti-oxLDL reactivity, which indicates that LPC may explain a significant part of the immune-stimulatory properties of oxLDL. LPC, being a lipid, is not likely to be an antigen itself.

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“…6), although it is widely unknown where, how, and to what extent oxidized LDL (oxLDL) is generated during atherogenesis. It was shown that oxLDL is involved in recruitment of monocytes and lymphocytes (113,134); for example, via stimulating endothelial cells and smooth muscle cells to secrete monocyte chemotactic protein-1 (MCP-1) (Fig. 6) (120,136).…”

Section: Protein Oxidation In Other Age-related Diseasesmentioning

confidence: 99%

Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

Reeg

Grune

2015

Antioxidants & Redox Signaling

166

134

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Significance: A constant accumulation of oxidized proteins takes place during aging. Oxidation of proteins leads to a partial unfolding and, therefore, to aggregation. Protein aggregates impair the activity of cellular proteolytic systems (proteasomes, lysosomes), resulting in further accumulation of oxidized proteins. In addition, the accumulation of highly crosslinked protein aggregates leads to further oxidant formation, damage to macromolecules, and, finally, to apoptotic cell death. Furthermore, protein oxidation seems to play a role in the development of various age-related diseases, for example, neurodegenerative diseases. Recent Advances: The highly oxidized lipofuscin accumulates during aging. Lipofuscin formation might cause impaired lysosomal and proteasomal degradation, metal ion accumulation, increased reactive oxygen species formation, and apoptosis. Critical Issues: It is still unclear to which extent protein oxidation is involved in the progression of aging and in the development of some age-related diseases. Future Directions: An extensive knowledge of the effects of protein oxidation on the aging process and its contribution to the development of age-related diseases could enable further strategies to reduce age-related impairments. Strategies aimed at lowering aggregate formation might be a straightforward intervention to reduce age-related malfunctions of organs. Antioxid. Redox Signal. 23, 239-255.

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Oxidatively modified low density lipoprotein is a chemoattractant for human T lymphocytes.

Cited by 245 publications

References 30 publications

SREC-II, a New Member of the Scavenger Receptor Type F Family, Trans-interacts with SREC-I through Its Extracellular Domain

SREC-II, a New Member of the Scavenger Receptor Type F Family, Trans-interacts with SREC-I through Its Extracellular Domain

Lysophosphatidylcholine Is Involved in the Antigenicity of Oxidized LDL

Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

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