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Infection and Immunity, July 2000, p. 4274-4281, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Influence of beta 2-Integrin Adhesion Molecule Expression and Pulmonary Infection with Pasteurella haemolytica on Cytokine Gene Expression in Cattle

Haa-Yung Lee,1,dagger Marcus E. Kehrli Jr.,1,Dagger Kim A. Brogden,2 Jack M. Gallup,3 and Mark R. Ackermann3,*

Metabolic Disease and Immunology Research Unit1 and Respiratory and Neurologic Disease Research Unit,2 National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, Iowa 50010, and Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa 50011-12503

Received 7 October 1999/Returned for modification 29 October 1999/Accepted 12 April 2000

beta 2-Integrins are leukocyte adhesion molecules composed of alpha (CD11a, -b, -c, or -d) and beta (CD18) subunit heterodimers. Genetic CD18 deficiency results in impaired neutrophil egress into tissues that varies between conducting airways and alveoli of the lung. In this study, we investigated whether CD18 deficiency in cattle affects proinflammatory cytokine (PIC) expression in pulmonary tissue after respiratory infection with Pasteurella haemolytica. Cattle were infected with P. haemolytica via fiberoptic deposition of organisms into the posterior part of the right cranial lung lobe. Animals were euthanized at 2 or 4 h postinoculation (p.i.), and tissues were collected to assess PIC gene expression using antisense RNA probes specific for bovine interleukin-1alpha (IL-1alpha ), IL-1beta , IL-6, gamma interferon (IFN-gamma ), and tumor necrosis factor alpha (TNF-alpha ) along with the beta -actin (beta -Act) housekeeping gene. Expression of PIC was induced at 2 h p.i. in P. haemolytica-infected cattle and continued to 4 h p.i. At 2 h p.i., induction of gene expression and increase of cells that expressed PIC were observed both in CD18+ and CD18- cattle after inoculation of P. haemolytica. The induction of gene expression with P. haemolytica inoculation was more prominent in CD18- cattle than in CD18+ cattle by comparison to pyrogen-free saline (PFS)-inoculated control animals. At 4 h p.i., however, the induction of PIC, especially IL-1alpha , IL-6, and IFN-gamma , in the lungs of CD18+ cattle inoculated with P. haemolytica was greater than that in lungs of the CD18- cattle. IFN-gamma and TNF-alpha genes were not increased in P. haemolytica-inoculated CD18- cattle lungs compared to the PFS-inoculated control lungs at 4 h p.i. In PFS-inoculated lungs, we generally observed a higher percentage of cells and higher level of gene expression in the lungs of CD18- cattle than in the lungs of CD18+ cattle, especially at 4 h p.i. The rate of neutrophil infiltration into the lungs of CD18- cattle at 2 h p.i. was significantly higher than that of CD18+ cattle; at 4 h p.i., there was no difference between the two groups. These data suggest that beta 2-integrins may contribute to the induction of expression of some PIC genes, as a consequence of P. haemolytica infection.


* Corresponding author. Mailing address: Department of Veterinary Pathology, 2738 Veterinary Medicine, Iowa State University, Ames, IA 50011-1250. Phone: (515) 294-3647. Fax: (515) 294-5423. E-mail: mackerma{at}iastate.edu.

dagger Present address: Department of Cell and Molecular Biology, House Ear Institute, Los Angeles, CA 90057.

Dagger Present address: Animal Health Research, Pfizer, Inc. Terre Haute, IN 47808.


Infection and Immunity, July 2000, p. 4274-4281, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.