Systemic Lymphocyte Activation Modulates the Severity of Diet-Induced Acute Pancreatitis in Mice

Abstract

To examine the role of lymphocyte activation in the development of local and systemic complications in acute pancreatitis, we compared disease severity of choline-deficient, 0.5% ethionine supplemented (CDE) diet-induced acute pancreatitis in T-and B-cell deficient SCID mice and immunocompetent C.B-17 mice. Twenty-five female SCID and 17 female C.B-17 mice were fasted for 24 h and fed a CDE diet for 72 h. Twenty SCID and 12 C.B-17 mice were bled and their organs removed for histologic evaluation. Five control animals of both kinds were fed a regular diet for 6 days. Lung, kidney, and pancreas were examined microscopically, and pancreatic damage scored. Apoptosis was detected by DNA nick-end labeling and confirmed by DNA laddering. Trypsinogenactivation peptide was measured by enzyme-linked immunosorbent assay (ELISA), and the catalytic activity of PLA2 was determined by a radiometric assay. Four-day mortality was 10% in SCID and 33% in C.B-17 mice, and 10-day mortality was 0 in SCID and 60% in C.B-17 mice. SCID mice had mild pulmonary damage, whereas pulmonary injury was severe in C.B-17 mice. Pancreatic damage was severe in both groups. Even though in situ staining of apoptotic cells was found in all pancreatitis animals, apoptosis was confirmed by DNA laddering only in C.B-17 mice. In SCID mice, apoptotic cell staining positively correlated with necrosis ( r = 0.91; p < 0.001).Plasma TAP and PLA2 catalytic activity did not differ significantly between the groups. In conclusion, the absence of T and B lymphocytes prevents severe pulmonary injury resulting from acute pancreatitis but does not influence pancreatic or renal damage. Our results suggest that systemic lymphocyte activation does not affect the initiating events that trigger pancreatic injury but modulates the systemic response, in particular, pulmonary injury caused by acute pancreatitis.

Apoptosis in the Peripheral Blood Mononuclear Cells as a Self-Limitation Process in Human Acute Pancreatitis

“…However, in a previous study [15], we reported that, during acute pancreatitis, in the patients with the highest values of CRP, the increase in serum levels of the soluble IL-2 receptor -considered a marker of lymphocyte activation and distant complications [27] peaked later, lasted longer, and was higher than in the patients with normal CRP values. The results of this report are in agreement with our present findings of sustained, moderately high levels of peripheral blood mononuclear cell apoptosis in patients with complicated acute pancreatitis, when lymphocyte activation is to be presumed, in parallel with the degree of the complications, overwhelming peripheral blood mononuclear cell apoptosis, even activated.…”

“…Induction of apoptosis in pancreatic acinar cells reduces the severity of experimental acute pancreatitis [17,[23][24][25]; besides, the resolution of the inflammatory responses developing in acute pancreatitis is dependent on neutrophil apoptosis which seems to be delayed during the illness [26]. Further, mortality rate and pulmonary injury are reduced in T-and B-cell-deficient mice with diet-induced acute pancreatitis [27], and depletion of circulating CD3+ lymphocytes has been found to reduce systemic complications in experimental pancreatitis [28]. Thus, systemic leucocyte activation or inactivation can modulate the severity of acute pancreatitis [19,26,27].…”

“…Further, mortality rate and pulmonary injury are reduced in T-and B-cell-deficient mice with diet-induced acute pancreatitis [27], and depletion of circulating CD3+ lymphocytes has been found to reduce systemic complications in experimental pancreatitis [28]. Thus, systemic leucocyte activation or inactivation can modulate the severity of acute pancreatitis [19,26,27]. The aim of this clinical study was to investigate whether, in addition to acinar pancreatic cell apoptosis [17,[23][24][25], peripheral blood mononuclear cell apoptosis is triggered during acute pancreatitis and, if so, whether this affects the course of the disease.…”

Human amniotic mesenchymal stem cells alleviate lung injury induced by ischemia and reperfusion after cardiopulmonary bypass in dogs

“…Semi-quantitative scoring of bleeding, edema, and inflammation of lung tissues was performed under high magnification (×400), using the Mayor and Osman score standard. 34,35 Assessment of hAMSC Localization in Lungs Lung tissues were harvested and fixed in 10% neutral buffer formalin. Immunohistochemical staining was performed as previously described.…”

Prophylactic Glycine Administration Attenuates Pancreatic Damage and Inflammation in Experimental Acute Pancreatitis

“…As one can expect, several studies aimed at targeting specific leukocyte subsets such as neutrophils [6,7,8,9], lymphocytes [10,11], or monocytes [12,13,14] and indeed demonstrated a significant improvement of pancreatic damage and mortality in various experimental pancreatitis models. However, a clinical translation of these achievements has yet to take place.…”