scholarly journals Proteomic Profiles of Exosomes of Septic Patients Presenting to the Emergency Department Compared to Healthy Controls

2020 ◽  
Vol 9 (9) ◽  
pp. 2930
Author(s):  
Daniel C. Morris ◽  
Anja K. Jaehne ◽  
Michael Chopp ◽  
Zhanggang Zhang ◽  
Laila Poisson ◽  
...  
Keyword(s):  
Emergency Department ◽  
Acute Phase ◽  
Serum Amyloid A ◽  
Tertiary Care ◽  
Differential Expression Analysis ◽  
Serum Amyloid ◽  
Care Hospital ◽  
Healthy Controls ◽  
Blood Draw ◽  
Amyloid A

Background: Septic Emergency Department (ED) patients provide a unique opportunity to investigate early sepsis. Recent work focuses on exosomes, nanoparticle-sized lipid vesicles (30–130 nm) that are released into the bloodstream to transfer its contents (RNA, miRNA, DNA, protein) to other cells. Little is known about how early changes related to exosomes may contribute to the dysregulated inflammatory septic response that leads to multi-organ dysfunction. We aimed to evaluate proteomic profiles of plasma derived exosomes obtained from septic ED patients and healthy controls. Methods: This is a prospective observational pilot study evaluating a plasma proteomic exosome profile at an urban tertiary care hospital ED using a single venipuncture blood draw, collecting 40 cc Ethylenediaminetetraacetic acid (EDTA) blood. Measurements: We recruited seven patients in the ED within 6 h of their presentation and five healthy controls. Plasma exosomes were isolated using the Invitrogen Total Exosome Isolation Kit. Exosome proteomic profiles were analyzed using fusion mass spectroscopy and Proteome Discoverer. Principal component analysis (PCA) and differential expression analysis (DEA) for sepsis versus control was performed. Results: PCA of 261 proteins demonstrated septic patients and healthy controls were distributed in two groups. DEA revealed that 62 (23.8%) proteins differed between the exosomes of septic patients and healthy controls, p-value < 0.05. Adjustments using the False Discovery Rate (FDR) showed 23 proteins remained significantly different (FDR < 0.05) between sepsis and controls. Septic patients and controls were classified into two distinct groups by hierarchical clustering using the 62 nominally DE proteins. After adjustment multiple comparisons, three acute phase proteins remained significantly different between patients and controls: Serum amyloid A-1, C-reactive protein and Serum Amyloid A-2. Inflammatory response proteins immunoglobulin heavy constant Δ and Fc-fragment of IgG binding protein were increased. Conclusion: Exosome proteomic profiles of septic ED patients differ from their healthy counterparts with regard to acute phase response and inflammation.

scholarly journals Investigation of the solubility and the potentials for purification of serum amyloid A (SAA) from equine acute phase serum – a pilot study

2013 ◽  
Vol 6 (1) ◽  
Author(s):  
Michelle B Christensen ◽  
Jens Christian Sørensen ◽  
Stine Jacobsen ◽  
Mads Kjelgaard-Hansen
Keyword(s):  
Pilot Study ◽  
Acute Phase ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Acute Phase Serum

scholarly journals Regulation of rabbit acute phase protein biosynthesis by monokines

1988 ◽  
Vol 253 (3) ◽  
pp. 851-857 ◽  
Author(s):  
A Mackiewicz ◽  
M K Ganapathi ◽  
D Schultz ◽  
D Samols ◽  
J Reese ◽  
...  
Keyword(s):  
Acute Phase ◽  
Serum Amyloid A ◽  
Interleukin 1 ◽  
Serum Amyloid ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Amyloid A ◽  
Primary Hepatocyte Cultures ◽  
Dose Dependent ◽  
Necrosis Factor

We defined the acute phase behaviour of a number of rabbit plasma proteins in studies (in vivo) and studied the effects of monokine preparations on their synthesis by rabbit primary hepatocyte cultures. Following turpentine injection, increased serum levels of C-reactive protein, serum amyloid A protein, haptoglobin, ceruloplasmin, and decreased concentrations of albumin were observed. In contrast to what is observed in man, concentrations of alpha 2-macroglobulin and transferrin were increased. Co-culture of primary hepatocyte cultures with lipopolysaccharide-activated human peripheral blood monocytes or incubation with conditioned medium prepared from lipopolysaccharide-activated human or rabbit monocytes resulted in dose-dependent induction of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and depression of albumin synthesis, while C-reactive protein synthesis and mRNA levels remained unchanged. A variety of interleukin-1 preparations induced dose-dependent increases in the synthesis and secretion of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and decreased albumin synthesis. Human recombinant tumour necrosis factor (cachectin) induced a dose-dependent increase in synthesis of haptoglobin and ceruloplasmin. In general, human interleukin-1 was more potent than mouse interleukin-1 and tumour necrosis factor. None of the monokines we studied had an effect on C-reactive protein synthesis or mRNA levels. These data confirm that C-reactive protein, serum amyloid A, haptoglobin and ceruloplasmin display acute phase behaviour in the rabbit, and demonstrate that, in contrast to their behaviour in man, alpha 2M and transferrin are positive acute phase proteins in this species. While both interleukin-1 and tumour necrosis factor regulate biosynthesis of a number of these acute phase proteins in rabbit primary hepatocyte cultures, neither of these monokines induced C-reactive protein synthesis. Comparison of these findings with those in human hepatoma cell lines, in which interleukin-1 does not induce serum amyloid A synthesis, suggests that the effect of interleukin-1 on serum amyloid A synthesis may be indirect.

In search of the “LINK”: Acute Phase Serum Amyloid A

2011 ◽  
Vol 216 (2) ◽  
pp. 266-268
Author(s):  
Sidika Karakas ◽  
Rami Mortada ◽  
Clinical Fellow
Keyword(s):  
Acute Phase ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Acute Phase Serum

Abstract 356: Serum Amyloid A Augments Aortic Aneurysm Formation Induced by Mineralocorticoid Receptor Agonists in the Presence of High Salt

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Nancy R Webb ◽  
Joanne M Wroblewski ◽  
Jenny Lutshumba ◽  
Maria C De Beer ◽  
Vicky P Noffsinger ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Acute Phase ◽  
Mineralocorticoid Receptor ◽  
Serum Amyloid A ◽  
The United States ◽  
High Salt ◽  
Serum Amyloid ◽  
Receptor Agonists ◽  
Amyloid A ◽  
Aneurysm Formation

Objectives: The annual mortality in the United States from ruptured aortic aneurysms is ~15000. Therapeutic interventions that prevent AAA progression and rupture remain to be identified. In humans, plasma concentrations of the acute phase reactant serum amyloid A (SAA) correlates with aortic dimensions before aneurysm formation. We have shown that endogenous SAA augments AAA in the well-established angiotensin II (AngII) infusion mouse model (unpublished data). Here we investigated whether endogenous SAA impacts aneurysm formation induced by deoxycorticosterone acetate (DOCA), a mineralocorticoid receptor agonist, in the presence of high salt. Approach and results: DOCA pellets (50mg, 21 day release) were implanted subcutaneously in the lateral dorsal region of 8-month old male C57BL/6 (SAAWT) mice and C57BL/6 mice lacking both acute phase SAA isoforms, SAA1.1 and SAA2.1 (SAAKO). The mice were also provided drinking water containing 0.9% NaCl and 0.2% KCl for 21 days (n = 7-8). As expected, DOCA + salt resulted in significantly increased systolic blood pressure, which was not affected by the absence of SAA. Unexpectedly SAAKO mice displayed a reduced urine output, accompanied by a reduced water intake. Plasma sodium and potassium concentrations in SAAWT and SAAKO mice were similar after treatment. The maximal luminal diameter of the abdominal aorta, as determined by ultrasound, was significantly lower in SAAKO mice compared to SAAWT mice after a 3-week DOCA + salt regime. Aneurysm incidence, determined by ultrasound and ex vivo analyses, was 67% for SAAWT mice and 25 % for SAAKO mice. Notably, plasma SAA was markedly increased in the SAAWT mice that formed aneurysms compared to those that did not. In SAAWT mice, immunohistochemical staining and in situ zymography identified SAA in aneurysmal aortic tissue, but not control aortas, that co-localized to regions of enhanced matrix metalloproteinase (MMP) activity, suggesting a role for SAA in MMP activation. Conclusions: We conclude that endogenous SAA augments aortic aneurysm formation induced by mineralocorticoid receptor agonists in the presence of high salt. Thus, SAA contributes to pathological processes leading to aortic aneurysm in two robust and mechanistically distinct animal models.

Serum Amyloid A, an Acute Phase Protein, Inhibits Platelet Activation

1991 ◽  
pp. 133-134 ◽  
Author(s):  
Shulamit Zimlichman ◽  
Abraham Danon ◽  
Ilana Nathan ◽  
Gabriel Mozes ◽  
Ruth Shainkin-Kestenbaum
Keyword(s):  
Platelet Activation ◽  
Acute Phase ◽  
Serum Amyloid A ◽  
Acute Phase Protein ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Phase Protein
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