Antibody blockade of α4β7 integrin ameliorates ischemia and reperfusion induced intestinal injury

Objective To determine the effects of antibody blockade of α4β7 integrin (LPAM-1) on the intestinal injury and systemic inflammatory response after ischemia and reperfusion injury (IR). Methods Mice were subjected to IR, with or without treatment with LPAM-1 monoclonal antibody. The intestinal injury and systemic inflammatory responsewas determined by examining lymphocyte infiltration, intestinal permeability, intestinal lactate levels, lung myeloperoxidase activity (MPO), lung vascular permeability and serum cytokine levels. Survival of the mice was determined over a one week time period. Results Antibody blockade of LPAM-1 attenuated the increased lymphocyte infiltration after IR [IR 8 h, Peyer patch: (4.5±0.6)×106 vs. (9.3±1.1)×106; lamina propria: (2.4±0.5)×106 vs. (5.1±0.9)×106; mucosa: (1.8±0.3)×106 vs. (2.9±0.6)×106; IR 24 h, Peyer patch: (3.9±0.8)×106 vs. (5.7±0.5)×106; lamina propria: (2.1±0.2)×106 vs. (2.9±0.4)×106; mucosa: (0.9±0.2)×106 vs. (1.4±0.4)×106]. Antibody blockade of LPAM-1 improved survivial (IR 168 h, 70% vs. 45%), gut permeability [IR 8 h, fluoresceinisothiocyanate dextran (FD4) clearance: (29.5±6.9) vs. (48.3±8.1) nl/(min·cm2); IR 24 h, (20.9±4.2) vs. (33.8±4.5) nl/(min·cm2)], intestinal lactate levels [IR 8 h, lactate level: (11.6±2.3) vs. (18.1±4.4) μg/mg; IR 24 h, (10.1±2.3) vs. (14.2±2.7) μg/mg], lung myeloperoxidase activity (IR 8 h, MPO activity: (7.6±1.7) vs. (13.3±2.9) U/g; IR 24 h, (4.8±0.9) vs. (8.6±1.5) U/g], lung vascular permeability [IR 8 h, A values: (4.7±0.6)×10-2 vs. (6.5±0.5)×10-2; IR 24 h, (3.4±0.5)×10-2 vs. (5.3±0.4)×10-2)] and serum levels of interleukine-1β (IL-1β), interleukine-6 (IL-6), tumor necrosis factor-α (TNF-α) [IR 8 h, IL-1β: (7.3±1.7) vs. (14.3±2.8) pg/mg; TNF-α: (1.4±1.3) vs. (2.0±0.3) pg/mg; IL-6: (4.6±5.5) vs. (7.4±0.8) pg/mg; IR 24 h, IL-1β: (7.6±1.2) vs. (10.1±1.6) pg/mg; TNF-α: (1.3±0.2) vs. (1.7±0.2) pg/mg; IL-6: (4.2±0.7) vs. (5.2±1.0) pg/mg]. Conclusion Antibody blockade of LPAM-1 attenuates intestinal injury and systemic inflammatory response after IR injury. Key words: Intestine; Ischemia; Reperfusion; Systemic inflammatory response syndrome