Albumin peptide: A molecular marker for trauma/hemorrhagic-shock in rat mesenteric lymph

Kaiser, Vicki L.; Sifri, Ziad C.; Senthil, Maheswari; Dikdan, George; Lu, Quan; Xu, Da-Zhong; Deitch, Edwin A.

doi:10.1016/j.peptides.2005.05.001

Cited by 17 publications

(15 citation statements)

References 33 publications

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“…Some of the observed PSML peculiar proteins have been already discussed above and might deserve further targeted investigations in the future, including proteases chymotrypsinogen and pepsin. The latter in particular might play a role in mediating albumin N-ter cleavage at acidic pH, resulting in the generation of a candidate biomarker for T/HS (34). …”

Section: Discussionmentioning

confidence: 99%

Lymph Is Not a Plasma Ultrafiltrate

Dzieciątkowska¹,

D’Alessandro²,

Moore³

et al. 2014

Shock

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Studies on animal models have documented a role for the water soluble protein fraction of mesenteric lymph as a conduit from hemorrhagic shock to acute lung injury and post-injury multiple organ failure. We hypothesize that mesenteric lymph is not an ultrafiltrate of plasma and contains specific protein mediators that may predispose patients to ALI/MOF. Mesenteric lymph and plasma were collected from critically ill or injured patients and from nine patients with lymphatic injuries, during semi-elective spine reconstruction, or immediately before organ donation. Proteomic analyses were performed through immuno-affinity depletion of the 14 most abundant plasma proteins, and GeLC-MS analyses. Overall, 548 proteins were identified in the patients undergoing semi-elective surgery, of which 155 were uniquely present in the lymph. In addition, the post-shock plasma proteome was characterized by peculiar features, suggesting that only a partial overlap exists between the plasma and mesenteric lymph from trauma patients. Differential proteins between the matched plasma and mesenteric lymph from trauma patients could be related to, coagulopathy and hypercoagulability, cell lysis, pro-inflammatory responses and immune system activation, extracellular matrix remodeling, lymph-specific immunomodulation and vascular hypoactivity/neoangiogenesis, and energy/redox metabolic adaptation to trauma. In conclusion, the proteome of mesenteric lymph is biologically different (in qualitative and quantitative terms) than that of a mere plasma ultrafiltrate.

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Section: Discussionmentioning

confidence: 99%

Lymph Is Not a Plasma Ultrafiltrate

Dzieciątkowska¹,

D’Alessandro²,

Moore³

et al. 2014

Shock

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“…These results are in line with previously reported studies showing selective truncation of albumin at position 24. 22,23 The N-terminal 24 -amino acid peptide has been described in various species as a major product of were labeled with PE-conjugated mouse anti-rat CD4, FITC-conjugated mouse anti-rat CD8, and FITC-conjugated mouse anti-rat CD11c. Labeled cells were analyzed using FACSAria.…”

Section: Discussionmentioning

confidence: 99%

Proteasomal Processing of Albumin by Renal Dendritic Cells Generates Antigenic Peptides

Macconi

Chiabrando

Schiarea

et al. 2009

Journal of the American Society of Nephrology

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The role of dendritic cells (DC) that accumulate in the renal parenchyma of non-immune-mediated proteinuric nephropathies is not well understood. Under certain circumstances, DC capture immunologically ignored antigens, including self-antigens, and present them within MHC class I, initiating an autoimmune response. We studied whether DC could generate antigenic peptides from the self-protein albumin. Exposure of rat proximal tubular cells to autologous albumin resulted in its proteolytic cleavage to form an N-terminal 24 -amino acid peptide (ALB1-24). This peptide was further processed by the DC proteasome into antigenic peptides that had binding motifs for MHC class I and were capable of activating syngeneic CD8 ϩ T cells. In vivo, the rat five-sixths nephrectomy model allowed the localization and activation of renal DC. Accumulation of DC in the renal parenchyma peaked 1 wk after surgery and decreased at 4 wk, concomitant with their appearance in the renal draining lymph nodes. DC from renal lymph nodes, loaded with ALB1-24, activated syngeneic CD8 ϩ T cells in primary culture. The response of CD8 ϩ T cells of five-sixths nephrectomized rats was amplified with secondary stimulation. In contrast, DC from renal lymph nodes of five-sixths nephrectomized rats treated with the proteasomal inhibitor bortezomib lost their capacity to stimulate CD8 ϩ T cells in primary and secondary cultures. These data suggest that albumin can be a source of potentially antigenic peptides upon renal injury and that renal DC play a role in processing self-proteins through a proteasome-dependent pathway.

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“…Should cytotoxic factors enter the general circulation from the intestine in sufficient amounts, they may cause remote cell death. Alternatively, cytotoxic factors might only act locally, within the intestinal tissue where pancreatic proteases are plentiful, in nearby or connected locations such as the peritoneum (36), or in the intestinal lymphatics (37,38). Even if the necrosis due to cytotoxic factors is limited to these regions, it may still contribute to inflammation in shock by release of inflammatory mediators from necrotic cells (11,39).…”

Section: Discussionmentioning

confidence: 99%

Pancreatic Enzymes Generate Cytotoxic Mediators in the Intestine

Penn¹,

Hugli²,

Schmid‐Schönbein³

2007

Shock

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Recent evidence indicates that shock is accompanied by a failure of the mucosal barrier in the intestine and entry of pancreatic digestive enzymes into the wall of the intestine. To investigate the formation of cytotoxic mediators produced by enzymatic digestion of the intestine, we applied homogenates of rat small intestinal wall to human neutrophils and used flow cytometry measurements of propidium iodide uptake to determine cytotoxicity. We show that homogenates of the small intestine after ischemia by occlusion of the superior mesenteric and celiac arteries for 3 h, but not without ischemia, are cytotoxic. Digestion of homogenates of nonischemic intestinal wall with purified trypsin, chymotrypsin, or elastase, proteases normally present in the intestinal lumen, yielded cytotoxic mediators. Before cell death, we saw cell damage in the form of bleb formation and flow cytometry measurements of cell size changes due to blebbing. Cytotoxicity was prevented by serine protease inhibition with phenylmethylsulfonyl fluoride (PMSF) before, but not after proteolytic digestion of the wall homogenates, indicating that enzymatic action of proteases on the homogenate is necessary for cytotoxicity. Cytotoxicity of wall homogenates digested by enzymes in the fluid collected from the lumen of the intestine was greater than digests by the individual purified proteases. Cytotoxicity is undetectable if digestive enzymes in the luminal fluid are inhibited with a combination of enzyme inhibitors PMSF and 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate before addition of wall homogenates. Passage of digested intestinal wall homogenates across a hydrophobic glass-fiber filter reduced cytotoxicity. Furthermore, we found that luminal fluid itself may be cytotoxic, possibly because of digestion of ingested food. To test whether digested food can be cytotoxic, we homogenized rat food and digested it in vitro with chymotrypsin or endogenous enzymes in luminal fluid. Cytotoxicity was significantly increased after digestion of food by luminal fluid compared with luminal fluid or undigested food. These results indicate the presence of a previously unknown mechanism for hemorrhagic necrosis in shock.

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Albumin peptide: A molecular marker for trauma/hemorrhagic-shock in rat mesenteric lymph

Cited by 17 publications

References 33 publications

Lymph Is Not a Plasma Ultrafiltrate

Lymph Is Not a Plasma Ultrafiltrate

Proteasomal Processing of Albumin by Renal Dendritic Cells Generates Antigenic Peptides

Pancreatic Enzymes Generate Cytotoxic Mediators in the Intestine

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