Activated Monocytes Induce Smooth Muscle Cell Death

Seshiah, Puvi; Kereiakes, Dean J.; Vasudevan, Sanjay S.; Lopes, Neuza; Su, Baogen Y.; Flavahan, Nicholas A.; Goldschmidt‐Clermont, Pascal J.

doi:10.1161/hc0202.102248

Cited by 69 publications

(21 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, activated monocyte-induced HRPE cell apoptosis was reduced by anti-CD18 (␤2 integrin) antibody. Our result is in agreement with previous reports that have shown the involvement of ␤2 integrins in smooth muscle cell apoptosis induced by monocytes activated with macrophage colony-stimulating factor; in HLA-DR-mediated monocyte apoptosis; in Fasmediated, monocyte-dependent, T lymphocyte apoptosis; in superantigen-induced death of specific CD4 ϩ T-lymphocytes; and in TNF-␣-induced neutrophil apoptosis (Damle et al, 1993b;Seshiah et al, 2002;Thibeault et al, 1999;Walzog et al, 1997;Wu et al, 1996). Previous studies have shown that the CD18-ICAM-1 adhesion pathway is important in the recognition of target cells and in monocyte-induced cytotoxicity of vascular endothelial cells and tumor cells (Bernasconi et al, 1991;Jonjic et al, 1992).…”

Section: Yoshida Et Alsupporting

confidence: 94%

“…Direct cell-to-cell contact has also been shown to influence cellular response, function, and survival in many kinds of cell types (Meszaros et al, 2000;Seshiah et al, 2002;Yoshida et al, 2001a). HRPE cells are frequently associated with monocytes in PVR, ARMD, and uveitis (Baudouin et al, 1992;Chan et al, 1985;Harper et al, 1992;Jerdan et al, 1989;Kampik et al, 1981;Vinores et al, 1990).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Activated Monocytes Induce Human Retinal Pigment Epithelial Cell Apoptosis Through Caspase-3 Activation

Yoshida

Elner

Bian

et al. 2003

Laboratory Investigation

View full text Add to dashboard Cite

Michigan SUMMARY:Dysfunction and loss of human retinal pigment epithelial (HRPE) cells is a significant component of many ocular diseases, in which mononuclear phagocyte infiltration at the HRPE-related interface is also observed. In this study, we investigated whether HRPE cell apoptosis may be induced by overlay of IFN-␥-activated monocytes. Human monocytes primed with IFN-␥ overlaid directly onto HRPE cells elicited significant increases in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive HRPE cells (p Ͻ 0.0001) and decreases of proliferating cell nuclear antigen-positive (p Ͻ 0.0001) HRPE cells. The activated monocytes also induced HRPE cell caspase-3 activation, which was inhibited by the caspase-3 inhibitor, Z-DEVD-fmk. However, co-incubations in which activated monocytes were prevented from direct contact with HRPE cells or in which the monocytes were separated from the HRPE cells after 30 minutes of direct contact, did not induce significant HRPE cell apoptosis. Function-blocking anti-CD18 and anti-intercellular adhesion molecule-1 (ICAM-1) antibodies significantly reduced activated monocyte-induced TUNEL-positive HRPE cells by 48% (p ϭ 0.0051) and 38% (p ϭ 0.046), respectively. Anti-CD18 and anti-ICAM-1 antibodies significantly inhibited caspase-3 activity by 56% (p Ͻ 0.0001) and 45% (p Ͻ 0.0001), respectively. However, antibodies to vascular cell adhesion molecule-1, TNF-␣, IL-1␤, or TNF-related apoptosisinducing ligand did not inhibit apoptosis or caspase-3 activation. Direct overlay of monocytes also induced reactive oxygen metabolites (ROM) within HRPE cells. The intracellular HRPE cell ROM production was inhibited by the anti-CD18 and anti-ICAM-1 antibodies, but not by superoxide dismutase, presumably due to its failure to penetrate into HRPE cells. Accordingly, neither superoxide dismutase nor N G -monomethyl-L-arginine had significant effects on HRPE cell apoptosis or caspase-3 activation. Our results suggest that activated monocytes may induce ROM in HRPE cells through cell-to-cell contact, in part via CD18 and ICAM-1, and promote HRPE cell apoptosis. These mechanisms may compromise HRPE cell function and survival in a variety of retinal diseases. (Lab Invest 2003, 83:1117-1129.

show abstract

Section: Yoshida Et Alsupporting

confidence: 94%

mentioning

confidence: 99%

Activated Monocytes Induce Human Retinal Pigment Epithelial Cell Apoptosis Through Caspase-3 Activation

Yoshida

Elner

Bian

et al. 2003

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…17 The reason is not quite clear, but it seems that SMCs play an important role in preserving the integrity of the extracellular matrix in the cap. 18,19 Furthermore, mechanical overstretching has proven to induce apoptosis in isolated vascular smooth muscle cells. 20 In our study, this phenomenon may be exemplified by the fact that high strain is correlated with a low amount of SMCs.…”

Section: Discussionmentioning

confidence: 99%

Characterizing Vulnerable Plaque Features With Intravascular Elastography

et al. 2003

View full text Add to dashboard Cite

Background-In vivo detection of vulnerable plaques is presently limited by a lack of diagnostic tools. Intravascular ultrasound elastography is a new technique based on intravascular ultrasound and has the potential to differentiate between different plaques phenotypes. However, the predictive value of intravascular elastography to detect vulnerable plaques had not been studied. Methods and Results-Postmortem coronary arteries were investigated with intravascular elastography and subsequently processed for histology. In histology, a vulnerable plaque was defined as a plaque consisting of a thin cap (Ͻ250 m) with moderate to heavy macrophage infiltration and at least 40% of atheroma. In elastography, a vulnerable plaque was defined as a plaque with a high strain region at the surface with adjacent low strain regions. In 24 diseased coronary arteries, we studied 54 cross sections. In histology, 26 vulnerable plaques and 28 nonvulnerable plaques were found. Receiver operator characteristic analysis revealed a maximum predictive power for a strain value threshold of 1.26%. The area under the receiver operator characteristic curve was 0.85. The sensitivity was 88%, and the specificity was 89% to detect vulnerable plaques. Linear regression showed high correlation between the strain in caps and the amount of macrophages (PϽ0.006) and an inverse relation between the amount of smooth muscle cells and strain (PϽ0.0001). Plaques, which are declared vulnerable in elastography, have a thinner cap than nonvulnerable plaques (PϽ0.0001). Conclusions-Intravascular elastography has a high sensitivity and specificity to detect vulnerable plaques in vitro.

show abstract

“…Indeed, FasL localizes to apoptotic SMC in advanced lesions and induces apoptosis of SMC in vitro (21,22). In addition, the cellular effectors of immune-mediated apoptosis in atherosclerotic plaques are likely T cells and macrophages, as these leukocytes have been implicated in SMC apoptosis and in the development of acute coronary syndromes (8,(23)(24)(25)(26)(27). Our association of granzyme B immunoreactivity with advanced atherosclerotic disease, and localization of granzyme B to apoptotic cells, suggests that this cytotoxic immune factor may further contribute to acute coronary syndromes through a similar mechanism as FasL.…”

Section: Discussionmentioning

confidence: 99%

Granzyme B in Atherosclerosis and Transplant Vascular Disease: Association with Cell Death and Atherosclerotic Disease Severity

et al. 2003

View full text Add to dashboard Cite

Apoptosis of intimal cells is an important contributor to the pathogenesis of atherosclerosis and transplant vascular disease (TVD).Since the activated immune response may be a key regulator of apoptosis in these lesions, we used immunohistochemistry to characterize the presence and localization of granzyme B, a major mediator of the cytotoxic immune response, in advanced atherosclerosis and TVD. Formalin-fixed, paraffin-embedded transverse sections from human left anterior descending coronary arteries were cut serially and stained with antibodies specific for granzyme B, smooth muscle ␣-actin, CD68, and CD3. The amount of granzyme B staining was semi-quantitated on a 0 -5؉/5؉ scale. Also, TUNEL staining and in situ hybridization was performed to visualize cells undergoing cellular damage suggestive of apoptosis, and to localize granzyme B mRNA, respectively. Granzyme B localization was similar in both diseases. This protease was absent in arteries with mild atherosclerosis, but was abundant in the intima and media of vessels with advanced atherosclerosis and TVD. Within the intima, granzyme B localized to TUNEL-positive foam cells surrounding lipid-rich atheromas. Staining of serial sections with granzyme B and either smooth muscle ␣-actin, anti-CD68, or anti-CD3 showed that granzyme B localized to smooth muscle cells, macrophages, and T-cells. Further, in situ hybridization for granzyme B mRNA in TVD cases localized its expression to infiltrating leukocytes and not foam cells. In conclusion, the presence of granzyme B in advanced atherosclerotic lesions and TVD is associated with increasing disease severity and cell death. These observations suggest that granzyme B-mediated apoptosis may contribute to the pathogenesis of these diseases.

show abstract

Activated Monocytes Induce Smooth Muscle Cell Death

Cited by 69 publications

References 36 publications

Activated Monocytes Induce Human Retinal Pigment Epithelial Cell Apoptosis Through Caspase-3 Activation

Activated Monocytes Induce Human Retinal Pigment Epithelial Cell Apoptosis Through Caspase-3 Activation

Characterizing Vulnerable Plaque Features With Intravascular Elastography

Granzyme B in Atherosclerosis and Transplant Vascular Disease: Association with Cell Death and Atherosclerotic Disease Severity

Contact Info

Product

Resources

About