The effects of neutrophil-mediated damage in acute Mannheimia (Pasteurella) haemolytica pneumonia
ICAM-1 expression in cattle with Bovine Leukocyte Adhesion Deficiency (BLAD) vs. cattle without BLAD in Mannheimia haemolytica (MH) pneumonia at 2 or 4 hours PI was assessed using in situ hybridization. There was a significant increase in ICAM-1 in bronchiolar and alveolar epithelium and endothelium of arteries and veins in both BLAD and non-BLAD MH-inoculated cattle compared to controls. Highest intensity of ICAM-1 was present in bronchioles while bronchi had the lowest. Most alveolar macrophages and neutrophils in infected lungs expressed ICAM-1. ICAM-1 expression was generally increased in infected BLAD cattle at 2 hours PI compared to non-BLAD but not at 4 hours PI. The increased expression of ICAM-1 during acute MH pneumonia in cattle suggests that ICAM-1 is upregulated and may play a role in leukocyte infiltration;Next we studied the effects of a selectin inhibitor, TBC1269, on conjugated dienes (CD), inducible nitric oxide synthase (iNOS), and programmed cell death (PCD) in MH pneumonia in neonatal calves at 6 hours PI. Levels of CD increased (P < 0.05) after MH-inoculation in treated and untreated calves. A significant increase in PCD of leukocytes was observed in treated compared with the untreated calves. iNOS was expressed by epithelial cells and leukocytes. Expression of iNOS was decreased in areas where airway epithelium was associated with abundant inflammation. The shift from epithelial to leukocyte iNOS production in inflamed areas suggests that there is a balance between free radical generation by leukocytes and epithelial cell NO production. This shift is unaffected by selectin inhibition;Finally, neutrophil infiltration and ICAM-1 expression after TBC1269 treatment was assessed. There were higher (P < 0.05) neutrophil counts in lungs of both treated and untreated calves compared with the control group at 2 or 6 hours PI as determined by image analysis. Bronchioles and alveoli had the highest counts compared to other microscopic locations. ICAM-1 was significantly greater in bronchiolar and alveolar epithelium in both treated and untreated calves. TBC1269-treatment did not affect ICAM-1 expression. This work suggests that selectin inhibition does not inhibit neutrophil infiltration. ICAM-1 and CD18-mediated adherence may override the role of selectins during MH pneumonia.