Mannheimia haemolytica infection of the lower respiratory tract of cattle results in a bronchofibrinous pneumonia characterized by massive cellular influx and lung tissue remodeling and scarring. Since altered levels of gelatinases and their inhibitors have been detected in a variety of inflammatory conditions and are associated with tissue remodeling, we examined the presence of gelatinases in lesional and nonlesional lung tissue obtained from calves experimentally infected with M. haemolytica. Lesional tissue had elevated levels of progelatinase A and B and active gelatinase A and B when compared with nonlesional tissue obtained from the same lung lobe. In vitro, M. haemolytica products stimulated production of gelatinase B, but not its activation, by bovine monocytes. Alveolar macrophages showed constitutive production of gelatinase B but no change in response to M. haemolytica products. Bovine neutrophils exposed to M. haemolytica products also released gelatinase B, and there was a significant increase in the activated form of this enzyme. These effects were virtually identical when recombinant O-sialoglycoprotease was used to stimulate these cells. M. haemolytica products also enhanced the expression by bovine monocytes and alveolar macrophages of the tissue inhibitor of metalloproteinase 1. Our results provide evidence that matrix metalloproteinases are activated in lung lesions from cattle with shipping fever and that M. haemolytica virulence products induce production, release, and especially activation of gelatinase B by bovine inflammatory cells in vitro.Bronchofibrinous pneumonia (shipping fever) is a respiratory disease in cattle that is characterized by cellular influx and interalveolar and interlobular fibrosis in the lungs of affected animals (3,7,18,20,64,65). Lung lesions consistently show areas of coagulation necrosis, extensive fibrin deposits, and intense cellular infiltration into the alveoli (5, 63, 65). Economic losses to the beef industry due to shipping fever are estimated at over one billion dollars per year in North America alone (64). Causes of this pneumonic condition are multifactorial, including a combination of stress or viral infection, with a final acute illness due most often to the bacteria Mannheimia (Pasteurella) haemolytica serotype A1 (16,39,64). M. haemolytica serotype A1 is a normal resident of the upper respiratory flora of most cattle, but when aspirated into the lower respiratory tract of immunocompromised animals, it is able to colonize the lungs and induce an inflammatory reaction (65).M. haemolytica was originally classified in the genus Pasteurella (50), but more recent genetic characterization has resulted in reclassification of 11 serotypes of biotype A in the new genus Mannheimia (4, 9). M. haemolytica is a trehalosenegative coccobacillus in which heat-stable lipopolysaccharide (LPS) constitutes 12 to 25% of the dried cell wall (66). During logarithmic growth, the bacteria produce and release a heatlabile exotoxin, termed leukotoxin (Lkt), and a heat-labile en...