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Infection and Immunity, July 2000, p. 4274-4281, Vol. 68, No. 7
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
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Influence of
2-Integrin Adhesion Molecule
Expression and Pulmonary Infection with Pasteurella
haemolytica on Cytokine Gene Expression in Cattle


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-1
(IL-1
), IL-1
, IL-6, gamma interferon (IFN-
),
and tumor necrosis factor alpha (TNF-
) along with the
-actin
(
-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-1
, IL-6,
and IFN-
, in the lungs of CD18+ cattle inoculated with
P. haemolytica was greater than that in lungs of the
CD18
cattle. IFN-
and TNF-
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
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.
Present address: Department of Cell and Molecular Biology, House
Ear Institute, Los Angeles, CA 90057.
Present address: Animal Health Research, Pfizer, Inc. Terre Haute,
IN 47808.
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