Neutrophil Apoptosis during the Development and Resolution of Oleic Acid-Induced Acute Lung Injury in the Rat

Hussain, Naveed; Wu, Fengying; Zhu, Li; Thrall, Roger S.; Kresch, Mitchell J.

doi:10.1165/ajrcmb.19.6.3118

Cited by 97 publications

(68 citation statements)

References 35 publications

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“…The serum collectin, MBL, did not significantly enhance phagocytosis. Because PMN apoptosis and subsequent phagocytosis by AMs are necessary for inflammation to be resolved (25)(26)(27), our data suggest that the pulmonary collectins may protect pulmonary tissue by facilitating the resolution of inflammation.…”

Section: Discussionmentioning

confidence: 83%

“…Several in vivo models of pulmonary injury demonstrate the importance of AM phagocytosis of apoptotic PMNs in the resolution of inflammation (25,26), and it has been suggested that chronic pulmonary inflammation may be a result of inefficient clearance of apoptotic PMNs (27). We hypothesize that when PMNs undergo apoptosis, the changes that occur at the PMN plasma membrane allow SP-A and SP-D to recognize them as nonself.…”

mentioning

confidence: 88%

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Surfactant Protein A Enhances Alveolar Macrophage Phagocytosis of Apoptotic Neutrophils

Schagat

Wofford

Wright

2001

The Journal of Immunology

192

128

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Surfactant protein A (SP-A) is an innate immune molecule that binds foreign organisms that invade the lungs and targets them for phagocytic clearance by the resident pulmonary phagocyte, the alveolar macrophage (AM). We hypothesized that SP-A binds to and enhances macrophage uptake of other nonself particles, specifically apoptotic polymorphonuclear neutrophils (PMNs). PMNs are recruited into the lungs during inflammation, but as inflammation is resolved, PMNs undergo apoptosis and are phagocytosed by AMs. We determined that SP-A increases AM phagocytosis of apoptotic PMNs 280 ± 62% above the no protein control value. The increase is dose dependent, and heat-treated SP-A still enhanced uptake, whereas deglycosylated SP-A had significantly diminished ability to enhance phagocytosis. Surfactant protein D also increased phagocytosis of apoptotic PMNs by ∼125%. However, other proteins that are structurally homologous to SP-A, mannose-binding lectin and complement protein 1q, did not. SP-A enhances phagocytosis via an opsonization-dependent mechanism and binds apoptotic PMNs ∼4-fold more than viable PMNs. Also, binding of SP-A to apoptotic PMNs does not appear to involve SP-A’s lectin domain. These data suggest that the pulmonary collectins SP-A and SP-D facilitate the resolution of inflammation by accelerating apoptotic PMN clearance.

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Section: Discussionmentioning

confidence: 83%

mentioning

confidence: 88%

Surfactant Protein A Enhances Alveolar Macrophage Phagocytosis of Apoptotic Neutrophils

Schagat

Wofford

Wright

2001

The Journal of Immunology

192

128

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“…The findings in the GTO-treated group are similar to those induced in OAinduced acute respiratory distress syndrome. 41,42 GTO treated rats also had renal failure evidenced by elevated serum blood urea nitrogen and TUNEL þ cells in the kidney tubules at the time of necropsy ( Figure 6B). Findings of drop out necrosis in these tubules supported progression to acute tubular necrosis.…”

Section: Intraductal Oaee Results In Lesser Systemic Injury Than Triomentioning

confidence: 98%

Fatty Acid Ethyl Esters Are Less Toxic Than Their Parent Fatty Acids Generated during Acute Pancreatitis

Patel

Durgampudi

Noel

et al. 2016

The American Journal of Pathology

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Although ethanol causes acute pancreatitis (AP) and lipolytic fatty acid (FA) generation worsens AP, the contribution of ethanol metabolites of FAs, ie, FA ethyl esters (FAEEs), to AP outcomes is unclear. Previously, pancreata of dying alcoholics and pancreatic necrosis in severe AP, respectively, showed high FAEEs and FAs, with oleic acid (OA) and its ethyl esters being the most abundant. We thus compared the toxicities of FAEEs and their parent FAs in severe AP. Pancreatic acini and peripheral blood mononuclear cells were exposed to FAs or FAEEs in vitro. The triglyceride of OA (i.e., glyceryl tri-oleate) or OAEE was injected into the pancreatic ducts of rats, and local and systemic severities were studied. Unsaturated FAs at equimolar concentrations to FAEEs induced a larger increase in cytosolic calcium, mitochondrial depolarization, and necro-apoptotic cell death. Glyceryl tri-oleate but not OAEE resulted in 70% mortality with increased serum OA, a severe inflammatory response, worse pancreatic necrosis, and multisystem organ failure. Our data show that FAs are more likely to worsen AP than FAEEs. Our observations correlate well with the high pancreatic FAEE concentrations in alcoholics without pancreatitis and high FA concentrations in pancreatic necrosis. Thus, conversion of FAs to FAEE may ameliorate AP in alcoholics. (Am J Pathol 2016, 186: 874e884; http://dx.doi.org/10.1016/j.ajpath.2015 Although fat necrosis has been associated with severe cases of pancreatitis for more than a century, 1,2 and alcohol consumption is a well-known risk factor for acute pancreatitis (AP), 3 only recently have we started understanding the mechanistic basis of these observations. 4e7 High amounts of unsaturated fatty acids (UFAs) have been noted in the pancreatic necrosis and sera of severe AP (SAP) patients by multiple groups. 8e12 These high UFAs seem pathogenically relevant because several studies show UFAs can cause pancreatic acinar injury or can worsen AP. 11e14 Ethanol may play a role in AP by distinct mechanisms, 3 including a worse inflammatory response to cholecystokinin, 4 increased zymogen activation, 15 basolateral enzyme release, 16 sensitization to stress, 7 FA ethyl esters (FAEEs), 17 cytosolic calcium, 18 and cell death. 19 Because the nonoxidative ethanol metabolite of fatty acids (FAs), FAEEs, were first noted to be elevated in the pancreata of dying alcoholics, they have been thought to play a role in AP. 17,19À22 Conclusive proof of the role of FAEEs in AP in comparison with their parent UFAs is lacking. Uncontrolled release of lipases into fat, whether in the pancreas or in the peritoneal cavity, may result in fat necrosis, UFA generation, which has been associated with SAP. 11,12 Pancreatic homogenates were also noted to have an ability to synthesize FAEEs from FAs and ethanol,20,23 and the putative enzyme for this was thought to be a lipase. 24,25 It has been shown that the FAEE synthase activity of the putative enzyme exceeds its lipolytic capacity by several fold. 25 Triglyceride (TG) forms >80% ...

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“…In animal models, induction of neutrophil apoptosis ameliorates ALI, 72 and the onset of neutrophil apoptosis coincides with the resolution phase of lung injury. 73 …”

Section: Epithelial Injurymentioning

confidence: 99%

Pathophysiology of Acute Lung Injury and the Acute Respiratory Distress Syndrome

Ware¹

2006

Semin Respir Crit Care Med

433

324

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Since the adult respiratory distress syndrome was first described substantial progress has been made in understanding the pathogenesis of this complex syndrome. This review summarizes our current understanding of the pathophysiology of what is now termed the acute respiratory distress syndrome (ARDS) and its less severe form acute lung injury (ALI), with an emphasis on cellular and molecular mechanisms of injury that may represent potential therapeutic targets. Although it is difficult to synthesize all of these abnormalities into a single, unified, pathogenetic pathway, a theme that emerges repeatedly is that of imbalance, be it between pro-and anti-inflammatory cytokines, oxidants and antioxidants, procoagulants and anticoagulants, neutrophil recruitment and activation and mechanisms of neutrophil clearance, or proteases and protease inhibitors. Future therapies aimed at restoring the overall balance of cytokines, oxidants, coagulants, and proteases may ultimately be successful where therapies that target individual cytokines or other mediators have not.

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Neutrophil Apoptosis during the Development and Resolution of Oleic Acid-Induced Acute Lung Injury in the Rat

Cited by 97 publications

References 35 publications

Surfactant Protein A Enhances Alveolar Macrophage Phagocytosis of Apoptotic Neutrophils

Surfactant Protein A Enhances Alveolar Macrophage Phagocytosis of Apoptotic Neutrophils

Fatty Acid Ethyl Esters Are Less Toxic Than Their Parent Fatty Acids Generated during Acute Pancreatitis

Pathophysiology of Acute Lung Injury and the Acute Respiratory Distress Syndrome

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