Influence of beta(2)-integrin adhesion molecule expression and pulmonary infection with Pasteurella haemolytica on cytokine gene expression in cattle

beta(2)-Integrins are leukocyte adhesion molecules composed of alpha (CD11a , -b, -c, or -d) and beta (CD18) subunit heterodimers. Genetic CD18 deficie ncy 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) ex pression in pulmonary tissue after respiratory infection with Pasteurella h aemolytica. Cattle were infected with P. haemolytica via fiberoptic deposit ion of organisms into the posterior part of the right cranial lung lobe. An imals 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 alpha (IL-1 alpha), IL-1 beta, IL-6, gamma interf eron (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) along with th e 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 P IC were observed both in CD18(+) and CD18(-) cattle after inoculation of P. haemolytica. The induction of gene expression with P. haemolytica inoculat ion 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., howe ver, the induction of PIG, especially IL-1 alpha, IL-6, and IFN-gamma, in t he 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 th e PFS-inoculated control lungs at 4 h p.i. In PFS-inoculated lungs, we gene rally observed a higher percentage of cells and higher level of gene expres sion in the lungs of CD18(-) cattle than in the lungs of CD18(+) cattle, es pecially 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(+) ca ttle; at I h p.i., there was no difference between the two groups. These da ta suggest that beta(2)-integrins may contribute to the induction of expres sion of some PIC genes, as a consequence of P. Haemolytica infection.