|Kehrli, Jr, Marcus|
Submitted to: Veterinary Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/19/1999
Publication Date: N/A
Citation: Interpretive Summary: Pasteurella haemolytica is the primary cause of a severe respiratory disease of dairy and beef cattle known as shipping fever or pneumonic pasteurellosis. During infection, large numbers of inflammatory cells migrate from the bloodstream into the lungs. These cells play an important role in controlling infection, but they also release products that damage lung tissue. If the degree of inflammatory cell migration can be controlled, it may be possible to reduce the level of lung injury. An understanding of the molecular mechanisms used by inflammatory cells to travel from the bloodstream into the lung could permit the development of treatments to interrupt this process. In some other mammalian species, it has been shown that the protein intercellular adhesion molecule-1 (ICAM-1), found on the surface of a variety of cells, is used by inflammatory cells as a door through which they are permitted to enter the lung. Expression and regulation of ICAM-1 in the lung of cattle has not been studied. Here we demonstrate that the expression of ICAM-1 is greatly increased in several cell types in the lung when calves are infected with P. haemolytica. This suggests that the large numbers of inflammatory cells in the lung of infected calves may have arrived there through the ICAM-1 pathway. However, large numbers of inflammatory cells were also found in the lung of calves that have a genetic defect in this pathway, making it unavailable for use. We conclude that inflammatory cells enter the lung of P. haemolytica-infected calves both through the ICAM-1 pathway as well as one or more additional pathways. This result will be useful in designing therapies to minimize the damage to lung that occurs during P. haemolytica infection.
Technical Abstract: The in situ expression of intercellular adhesion molecule-1 (ICAM-1) mRNA in lung tissues of Holstein calves with bovine leukocyte adhesion deficiency (BLAD) was compared to age-matched non-BLAD Holstein calves by in situ hybridization. Twenty-four Holstein calves were randomly assigned to one of two experimental groups and inoculated intrabronchially with Pasteurella haemolytica or pyrogen-free saline. Lung tissues were collected and fixed in 10% neutral formalin at 2 or 4 hours post- inoculation. The expression and distribution of ICAM-1 mRNA in the different cell types of the lung tissue was detected by in situ hybrid- ization with a 307 base pair bovine ICAM-1 riboprobe. In lungs of both non-BLAD and BLAD saline-inoculated calves, ICAM-1 expression was present in epithelial cells but occurred in <30% of cells in bronchi, bronchioles, and alveoli. ICAM-1 expression in vascular endothelial cells was present in <30% of cells in pulmonary arteries and veins. The expression of ICAM- was significantly greater (>60% of cells) in bronchiolar and alveolar epithelial cells and pulmonary endothelial cells of arteries and veins in both BLAD and non-BLAD calves inoculated with P. haemolytica. Bronchiolar epithelium had the highest intensity of mRNA expression and highest per- centage of cells that were stained, while bronchial epithelium was the lowest. Alveolar macrophages and neutrophils in infected lungs also expressed ICAM-1. The increased expression of ICAM-1 during acute P. haemolytica pneumonia in calves suggests that ICAM-1 may play a role in leukocyte infiltration. The extent of ICAM-1 expression in P. haemolytica- inoculated calves with BLAD was similar to non-BLAD calves, which suggests that leukocyte adhesion deficiency does not enhance ICAM-1 expression.