Serum amyloid A is an activator of PMN antimicrobial functions: induction of degranulation, phagocytosis, and enhancement of anti-<i>Candida</i> activity

Badolato, Raffaele; Wang, Ji Ming; Stornello, Sarah-Linnéa; Ponzi, A. Negro; Duse, Marzia; Musso, Tiziana

doi:10.1002/jlb.67.3.381

Cited by 82 publications

(48 citation statements)

References 42 publications

(49 reference statements)

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“…SAA may bind and transport cholesterol into aortic smooth muscle cells (28). Additionally, SAA also promotes monocyte chemotaxis and adhesion (4). These data suggest that SAA is a biomarker and biomediator for cardiovascular disease.…”

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confidence: 69%

Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells

Wang¹,

Chai²,

Wang³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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. Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells. Am J Physiol Heart Circ Physiol 295: H2399 -H2408, 2008. First published October 17, 2008 doi:10.1152/ajpheart.00238.2008.-The objective of this study was to determine the effects and mechanisms of serum amyloid A (SAA) on coronary endothelial function. Porcine coronary arteries and human coronary arterial endothelial cells (HCAECs) were treated with SAA (0, 1, 10, or 25 g/ml). Vasomotor reactivity was studied using a myograph tension system. SAA significantly reduced endothelium-dependent vasorelaxation of porcine coronary arteries in response to bradykinin in a concentration-dependent manner. SAA significantly decreased endothelial nitric oxide (NO) synthase (eNOS) mRNA and protein levels as well as NO bioavailability, whereas it increased ROS in both artery rings and HCAECs. In addition, the activities of internal antioxidant enzymes catalase and SOD were decreased in SAA-treated HCAECs. Bio-plex immunoassay analysis showed the activation of JNK, ERK2, and IB-␣ after SAA treatment. Consequently, the antioxidants seleno-L-methionine and Mn(III) tetrakis-(4-benzoic acid)porphyrin and specific inhibitors for JNK and ERK1/2 effectively blocked the SAA-induced eNOS mRNA decrease and SAA-induced decrease in endothelium-dependent vasorelaxation in porcine coronary arteries. Thus, SAA at clinically relevant concentrations causes endothelial dysfunction in both porcine coronary arteries and HCAECs through molecular mechanisms involving eNOS downregulation, oxidative stress, and activation of JNK and ERK1/2 as well as NF-B. These findings suggest that SAA may contribute to the progress of coronary artery disease. endothelial nitric oxide synthase; reactive oxygen species; antioxidant; mitogen-activated protein kinase; nuclear factor-B IT IS WELL KNOWN that inflammation plays a crucial role in the pathogenesis of atherosclerosis (29). Serum amyloid A (SAA) belongs to a family of the major acute-phase proteins in vertebrates and was discovered in 1971 as a principal constituent within the amyloid deposits of patients with persistent inflammation (31,44,47). Recent studies have shown that increased levels of SAA are strongly associated with many inflammation conditions including cardiovascular diseases (11,22,32). For example, SAA levels have also been correlated with the severity of human coronary artery atherosclerosis (32) and many cardiovascular risk factors including obesity, insulin resistance, diabetes (26), and rheumatoid arthritis (50). SAA can bind to extracellular vascular glycans and impair the ability of HDL to promote cholesterol efflux from macrophages (3). Lewis et al. (27) reported that circulating SAA levels, but not lipid levels, were strongly associated with the extent of aortic atherosclerosis in a mouse model, and SAA colocalized with apolipoprotein A-I and proteoglycans in atherosclerotic lesions. SAA may bind and transport cholesterol into aortic smooth muscle cells (28). Ad...

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mentioning

confidence: 69%

Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells

Wang¹,

Chai²,

Wang³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…However, as the major stimulus for the secretion of SAA are many proinflammatory cytokines such as IL-1, IL-6, IL-8 and TNF-a, 21 it is assumed that measuring SAA can give us an indication of the total effect of all the inflammatory cytokines that individually can induce the production of SAA. The finding that SAA specifically activates polymorphonuclear antimicrobial function by inducting degranulation, phagocytosis and enhancement of anticandidal activity, 22 can partially explain the differences in the dynamics of SAA and CRP.…”

Section: Discussionmentioning

confidence: 98%

Serum amyloid A: an early and accurate marker of neonatal early-onset sepsis

et al. 2007

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Objectives: To evaluate the accuracy of serum amyloid A (SAA), an acute phase protein in the detection of neonatal early-onset sepsis, by means of a fast automated SAA kit.Study Design: Full-term infants <72 h of age, who had risk factors and/or were suspected of having sepsis, were eligible for study. The levels of SAA were taken at 0, 24 and 48 h post sepsis evaluation. Thirty matched infants served as a control group for comparing SAA concentrations.Results: Of 104 infants eligible for entry to the study, 23 had sepsis and 81 had not sepsis. The SAA levels of the septic group were significantly higher than those of the nonseptic group at 0, 24 and 48 h (P<0.01 for all time points). In comparison with C-reactive protein (CRP), SAA levels rose earlier and in a sharper manner, had higher levels and returned faster to normal values in infants with early onset sepsis. At 0 h post-sepsis evaluation, serum SAA had an overall better diagnostic accuracy for predicting early onset sepsis than CRP (sensitivity (96 vs 30%), specificity (95 vs 98%), positive predictive value (85 vs 78%), negative predictive value (99 vs 83%), positive likelihood ratio (19 vs 12), and negative likelihood ratio (0.05 vs 0.71).Conclusions: SSA is advocated as an inflammatory marker of neonatal early-onset sepsis.

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“…Recently, Raynes and coworkers discovered that SAA binds rapidly and firmly to a surprisingly large number of Gram-negative bacteria through the outer member protein A (36). Stimulation of polymorphonuclear cells with SAA increases the secretion of lactoferrin and enhances polymorphonuclear cell phagocytic activity against Candida albicans (37), suggesting that SAA is an important molecule in innate immunity. We observed an impressive increase in the expression of SAA by dsRNA and FP individually, and the combination of dsRNA and FP induced the greatest increase of SAA expression by epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoids Enhance or Spare Innate Immunity: Effects in Airway Epithelium Are Mediated by CCAAT/Enhancer Binding Proteins

Zhang

Truong-Tran

Tancowny

et al. 2007

The Journal of Immunology

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Although it is widely accepted that glucocorticoids (GC) are a mainstay of the treatment of diseases characterized by airway inflammation, little is known about the effects of GC on local innate immunity. In this article, we report that respiratory epithelial cells manifested a local “acute phase response” after stimulation with TLR activation and TNF-α and that GC spared or enhanced the epithelial expression of molecules that are involved in host defense, including complement, collectins, and other antimicrobial proteins. As expected, GC inhibited the expression of molecules responsible for inflammation such as cytokines (IFNβ and GM-CSF) and chemokines (RANTES and IL-8). Studies using Western blotting, EMSA, and functional analysis indicated that the selective effects of GC are mediated through activation of the transcription factor C/EBP. Knockdown of C/EBPβ by small interfering RNA blocked the enhancement by GC of host defense molecule expression but had no effect on inflammatory gene expression. These results suggest that GC spare or enhance local innate host defense responses in addition to exerting anti-inflammatory actions. It is possible that the known ability of GC to reduce the exacerbation of diseases in which infectious organisms serve as triggering factors (e.g., asthma, allergic bronchopulmonary aspergillosis, and chronic obstructive pulmonary disease) may result in part from enhanced innate immune responses in airway mucosa.

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Serum amyloid A is an activator of PMN antimicrobial functions: induction of degranulation, phagocytosis, and enhancement of anti-Candida activity

Cited by 82 publications

References 42 publications

Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells

Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells

Serum amyloid A: an early and accurate marker of neonatal early-onset sepsis

Glucocorticoids Enhance or Spare Innate Immunity: Effects in Airway Epithelium Are Mediated by CCAAT/Enhancer Binding Proteins

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