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Title: INFLUENCE OF BETA2-INTEGRIN ADHESION MOLECULE EXPRESSION AND PULMONARY INFECTION WITH PASTEURELLA HAEMOLYTICA ON CYTOKINE GENE EXPRESSION IN CATTLE

Author
item LEE, HAA-YUNG - HOUSE EAR INSTIT., CALIF.
item KEHRLI, MARCUS - PFIZER, INC., INDIANA
item Brogden, Kim
item GALLUP, JACK - IA STATE UNIV., AMES, IA
item ACKERMANN, MARK - IA STATE UNIV., AMES, IA

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/12/2000
Publication Date: 7/1/2000
Citation: N/A

Interpretive Summary: Respiratory tract diseases are a leading cause of loss from disease in the cattle, sheep, and goat industries. Annual loss in the United States is estimated to exceed one billion dollars. Losses are from mortality, reduced feed efficiency, and slaughter condemnations, as well as prevention and treatment measures. Currently, not all the factors leading to the development of pneumonia are known by scientists and veterinarians. In this study, the role of a leukocyte adhesion molecule in the pathogenesis of pneumonia was assessed by comparing acute phase cytokine expression in normal cattle and cattle deficient in the leukocyte adhesion molecule after infection with the bacterium, Pasteurella haemolytica. This data showed that normal, infected cattle expressed acute phase cytokines, whereas the infected cattle deficient in the leukocyte adhesion molecule did not. These results show that the leukocyte adhesion molecule is important in the eimmune response of normal, infected animals, as cattle deficient in the molecule are unable to clear invading pathogens efficiently because of the immune system impairment. Corollary benefits of this research include an increase in the profitability and international competitiveness of the U. S. cattle industry, a stronger rural economy, and a continued supply of inexpensive, wholesome beef and beef products for the American consumer.

Technical Abstract: Beta2 (B2)-integrins are leukocyte adhesion molecules composed of alpha and beta (CD18) subunits. Genetic CD18 deficiency (CD18-) results when impaired neutrophils egress into tissues of the lung. In this study, we investigated whether or not CD18 deficiency in cattle affects acute phase cytokine (APC) expression in pulmonary tissue after infection with Pasteurella haemolytica. Cattle were infected and euthanized at 2 or 4 hours post-inoculation (PI) to assess APC gene expression. In the CD18- cattle, expression of IFN-gamma and TNF-alpha genes were not increased in infected lung compared to saline inoculated control lungs. In control lungs, a higher percentage of cells and higher level of gene expression were observed in the lungs of CD18- cattle than in the lungs of CD18+ cattle. Expression of APC was induced at 2 h PI in P. haemolytica infected cattle and increased at 4 h PI. At 2 h PI, levels of gene expression between CD18+ and CD18- cattle were not significantly different. At 4 h PI, the lungs of CD18+ cattle expressed stronger signals of IL-1alpha and IFN-gamma than that of the CD18- cattle. When compared to control lung tissues, the increase of IL-1 alpha, IL-6, IFN-gamma, and TNF-alpha gene expression in the lung of CD18+ cattle at 4 h PI with P. haemolytica was greater than that of CD18- cattle in terms of either intensity of gene expression or percentage of APC gene expression positive cells. The rate of neutrophil infiltration into the lungs of the CD18-cattle at 2 h PI with P. haemolytica was significantly higher than that of CD18+ cattle, but at 4 h PI, there was no difference between the two groups. These data suggest that Beta2-integrins may contribute to the induction of some APC gene expression as a consequence of P. haemolytica infection.