Lung Inflammation Associated With Clinical Acute Necrotizing Pancreatitis in Dogs

Although dogs with acute necrotizing pancreatitis (ANP) can develop respiratory complications, there are no data describing lung injury in clinical cases of ANP in dogs. Therefore, we conducted a study to characterize lung injury and determine if pulmonary intravascular macrophages (PIMs) are induced in dogs with ANP ( n = 21) compared with control dogs ( n = 6). Two pathologists independently graded histologic sections of pancreas from clinical cases to characterize the severity of ANP (total scores of 3–10) compared with controls showing histologically normal pancreas (total scores of 0). Based on histological grading, lungs from dogs with ANP showed inflammation (median score, 1.5; range, 0–3), but the scores did not differ statistically from the control lungs (median score, 0.5; range, 0–2). A grid intersects-counting method showed an increase in the numbers of MAC387-positive alveolar septal mononuclear phagocyte profiles in lungs of dogs with ANP (ratio median, 0.0243; range, 0.0093–0.0734, with 2 outliers at 0.1523 and 0.1978) compared with controls (ratio median, 0.0019; range, 0.0017–0.0031; P < .0001). Only dogs with ANP showed labeling for von Willebrand factor in alveolar septal capillary endothelial cells, septal inflammatory cells, and alveolar macrophages. Toll-like receptor 4 and interleukin 6 were variably expressed in alveolar macrophages and septal inflammatory cells in lungs from both ANP and control dogs. Inducible nitric oxide synthase was detected in alveolar macrophages of dogs with ANP only. These data show that dogs with ANP have lung inflammation, including the recruitment of PIMs and expression of inflammatory mediators.

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A crucial role of nitric oxide in acute lung injury secondary to the acute necrotizing pancreatitis

Human & Experimental Toxicology ◽

10.1177/0960327110361760 ◽

2010 ◽

Vol 29 (4) ◽

pp. 329-337 ◽

Cited By ~ 16

Author(s):

Shi Cheng ◽

Wen-Mao Yan ◽

Bin Yang ◽

Jing-dong Shi ◽

Mao-min Song ◽

...

Keyword(s):

Nitric Oxide ◽

Lung Injury ◽

Lung Inflammation ◽

Necrotizing Pancreatitis ◽

Acute Necrotizing Pancreatitis ◽

No Production ◽

Acute Lung Inflammation ◽

Tnf Α ◽

Acute Necrotizing

To investigate the role of nitric oxide (NO) in acute lung inflammation and injury secondary to acute necrotizing pancreatitis (ANP), 5% sodium taurocholate was retrogradely injected into the biliopancreatic duct of rats to ANP model. These ANP rats were given L-Arginine (L-Arg, 100 mg/kg), L-NAME (10 mg/kg), or their combination by intraperitoneal injection 30 min prior to ANP induction. At 1, 3, 6, and 12 hours after ANP induction, lung NO production, and inducible NO synthase (iNOS) expression were measured. Lung histopathological changes, bronchoalveolar lavage (BAL) protein concentration, proinflammatory mediators tumor necrotic factor alpha (TNF-α), and lung tissue myeloperoxidase (MPO) activity were examined. Results showed that NO production and iNOS mRNA expression in alveolar macrophages (AMs) were significantly increased along with significant increases in lung histological abnormalities and BAL proteins in the ANP group, all of which were further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These markers were slightly attenuated by pretreatment with combination of L-Arg + L-NAME, suggesting that NO is required for initiating the acute lung damage in ANP rats, and also that L-Arg-enhanced lung injury is mediated by its NO generation rather than its direct effect. MPO activity and TNF-α expression in lung were upregulated in the ANP rats and further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These results suggest that overproduction of NO mediated by iNOS in the lung is required for the acute lung inflammation and damage secondary to ANP.

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