Volume 116, Issue 3, Pages 694-701 (March 1999) The role of intercellular adhesion molecule 1 and neutrophils in acute pancreatitis and pancreatitis-associated lung injury  Jean-Louis Frossard, Ashok Saluja, Lakshmi Bhagat, Hong Sik Lee, Madhav Bhatia, Bernd Hofbauer, Michael L. Steer  Gastroenterology  Volume 116, Issue 3, Pages 694-701 (March 1999) DOI: 10.1016/S0016-5085(99)70192-7 Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 1 Immunolocalization of ICAM-1. Mice were given 12 hourly injections of (A and D) saline or (B, C, E, and F) saline containing cerulein (50 μg/kg intraperitoneally). ICAM-1 was immunolocalized, as described in the text, in samples from the (A–C) pancreas or (D–F) lung (brown stain in photomicrographs). In control, wild-type mice given injections of saline, small amounts of ICAM-1 are noted in the endothelial cells lining vascular spaces in the (A) pancreas and (D) lung. After cerulein administration to wild-type mice, ICAM-1 expression on vascular surfaces (arrows) in both the (B) pancreas and (E) lung is markedly increased. ICAM-1 expression is not detected in either the (C) pancreas or (F) lung of mice genetically incapable of expressing ICAM-1, even after cerulein administration (original magnification: pancreas, 600×; and lung, 400×). Gastroenterology 1999 116, 694-701DOI: (10.1016/S0016-5085(99)70192-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 2 Effects of ICAM-1 deficiency and neutrophil depletion on pancreas and lung MPO activity during secretagogue-induced pancreatitis. Mice were given 12 hourly injections of cerulein (50 μg/kg intraperitoneally) or saline (control) and killed 1 hour later. (A) Pancreas and (B) lung MPO activity were quantitated as described in the text. 2, Wild-type ICAM-1–sufficient animals; ■, ICAM-1–deficient animals. ANS was administered as described in the text. Results shown are means ± SEM for 18 or more animals in each group. *P < 0.01, ICAM-1–deficient animals compared with ICAM-1–sufficient animals. Gastroenterology 1999 116, 694-701DOI: (10.1016/S0016-5085(99)70192-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 3 Effects of ICAM-1 deficiency and neutrophil depletion on the severity of secretagogue-induced pancreatitis. Animal groups are as described in Figure 2. 2, Wild-type ICAM-1–sufficient animals; ■, ICAM-1–deficient animals. (A) Serum amylase activity, (B) pancreas water content, and (C) acinar cell necrosis were quantitated as described in the text. Results shown are means ± SEM for 10 or more animals in each group. *P < 0.05, ICAM-1–deficient animals compared with ICAM-1–sufficient animals. Gastroenterology 1999 116, 694-701DOI: (10.1016/S0016-5085(99)70192-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 4 Effects of ICAM-1 deficiency and neutrophil depletion on pulmonary microvascular permeability during secretagogue-induced pancreatitis. Animal groups are as described in Figure 2. 2, Wild-type ICAM-1–sufficient animals; ■, ICAM-1–deficient animals. FITC-labeled albumin was administered intravenously 2 hours before animals were killed, and leakage of FITC-labeled albumin into the bronchoalveolar space was quantitated as described in the text. Results are expressed as the ratio of FITC-labeled albumin in BAL fluid and serum. Results shown are means ± SEM for 14 or more animals in each group. *P < 0.01, ICAM-1–deficient animals compared with ICAM-1–sufficient animals. Gastroenterology 1999 116, 694-701DOI: (10.1016/S0016-5085(99)70192-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 5 Effects of ICAM-1 deficiency on the severity of diet-induced pancreatitis. Mice were fed either the CDE diet or regular laboratory chow for 2 days and killed as described in the text. 2, ICAM-1–sufficient animals fed regular laboratory chow; ■, ICAM-1–deficient animals fed regular laboratory chow; ▨, ICAM-1–sufficient animals fed CDE diet; ▩, ICAM-1–deficient animals fed CDE diet. Results expressed as a percent of the value noted when ICAM-1–sufficient mice were fed the CDE diet (i.e., maximal value). Results shown are means ± SEM values for 18 or more animals in each group. *P < 0.05, ICAM-1–deficient animals compared with ICAM-1–sufficient animals. Gastroenterology 1999 116, 694-701DOI: (10.1016/S0016-5085(99)70192-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 6 Effects of ICAM-1 deficiency on lung injury of diet-induced pancreatitis. Lung MPO activity and pulmonary microvascular permeability index to FITC-labeled albumin were quantitated as described in the text. Results are expressed as a percent of the value noted when ICAM-1–sufficient mice were fed the CDE diet (i.e., maximal value). Results shown are means ± SEM values for 12 or more animals in each group. *P < 0.05, ICAM-1–deficient animals compared with ICAM-1–sufficient animals. 2, ICAM-1–sufficient animals fed regular laboratory chow; ■, ICAM-1–deficient animals fed regular laboratory chow; ▨, ICAM-1–sufficient animals fed CDE diet; ▩, ICAM-1–deficient animals fed CDE diet. Gastroenterology 1999 116, 694-701DOI: (10.1016/S0016-5085(99)70192-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 7 Effects of ICAM-1 deficiency on mortality rate of diet-induced pancreatitis. ICAM-1–sufficient mice (●) and ICAM-1–deficient mice (○) were fasted for 24 hours, fed the CDE diet for 48 hours, and given regular laboratory chow for 3 days to allow estimation of mortality rate. Results shown are for 26 animals in each group. When subjected to Kaplan–Meier analysis, the mortality rate for ICAM-1–sufficient mice was significantly greater (P < 0.05) than that for ICAM-1–deficient animals. Gastroenterology 1999 116, 694-701DOI: (10.1016/S0016-5085(99)70192-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions