Passage of CD18- and CD18+ Bovine Neutrophils into Pulmonary Alveoli during Acute Pasteurella haemolytica Pneumonia

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Abstract
CD18 is a subunit for three β2 integrin molecules (Mac-1, p150, 95, LFA-1), which are expressed on the plasma membrane of neutrophils. These molecules mediate passage of neutrophils into sites of infection. In children and animals that lack CD18 expression, neutrophil infiltration is impaired in most tissues. However, in lung, CD18-neutrophils have been identified in the airway spaces during spontaneous episodes of pneumonia. To determine whether CD18 is vital for passage through the pulmonary alveolar wall, lung lobes of cattle with neutrophils that were deficient in CD18 expression (CD18-) and cattle with normal CD18 expression (CD18+) were inoculated with Pasteurella haemolytica by fiberoptic bronchoscopy; control lobes were inoculated with pyrogen-free saline (PFS). Neutrophil passage into alveolar lumina at 4 and 6 hours postinoculation was measured by computerized image analysis. Blood levels of neutrophils for CD18- cattle ranged from 12- to 26-fold higher than for CD18+ cattle prior to inoculation, and counts in both groups rose slightly postinoculation. In P. haemolytica-inoculated lobes, total numbers of neutrophils in alveolar lumina of the two groups were similar. An increase in the number of neutrophils in the alveolar wall was fourfold greater in CD18- cattle than in CD18+ cattle. In PFS-inoculatad lobes, the number of neutrophils in the alveolar wall was sixfold higher in CD18 cattle than in CD18+ cattle. This work shows that by 4 and 6 hours, CD18 neutrophils enter the alveolar lumen at a rate similar to that in CD18+ cattle. Higher numbers of CD18- neutrophils are present in the alveolar wall of control (PFS) and bacteria-inoculated lobes. Thus, the CD18- cells are increased in the walls of alveoli and numbers of neutrophils that enter the alveolar lumen are similar in CD18+ and CD18- cattle.