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Infection and Immunity, February 1999, p. 659-663, Vol. 67, No. 2
Department of Veterinary Pathology, College
of Veterinary Medicine, Iowa State University, Ames, Iowa
50011-1250,1 and
Ruminant Respiratory
and CNS Diseases Unit2 and
Immunology of
Ruminant Perinatal Diseases,3 USDA
Agricultural Research Service
Received 20 July 1998/Returned for modification 2 September
1998/Accepted 26 October 1998
Pasteurella haemolytica is an important respiratory
pathogen of cattle that incites extensive infiltrates of
neutrophils into the lung. In addition to the parenchymal
damage caused by factors released by P. haemolytica,
neutrophils contribute to the pathologic changes in the lungs.
Molecules which mediate neutrophil infiltration into the lungs during
P. haemolytica pneumonia are poorly characterized. To
determine whether the CD18 family (
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Induction of CD18-Mediated Passage of Neutrophils
by Pasteurella haemolytica in Pulmonary Bronchi
and Bronchioles
and
National Animal Disease Center, Ames,
Iowa 50010
2-integrin) of
leukocyte adhesion molecules mediates initial passage of neutrophils
into the pulmonary bronchi and bronchioles of lungs infected with
P. haemolytica, three Holstein calves homozygous for bovine
leukocyte adhesion deficiency (BLAD) (CD18-deficient neutrophils), and
three age- and breed-matched control calves (normal CD18 expression) were inoculated with P. haemolytica A1 via a fiberoptic
bronchoscope and euthanized at 2 h postinoculation. Sections of
lung were stained for neutrophils, and the intensity of neutrophilic
infiltration was determined by computerized image analysis.
Significantly fewer (P < 0.05) neutrophils
infiltrated the lumen, epithelium, and adventitia of bronchioles and
bronchi in lungs of calves with BLAD compared to normal calves, which
had dense infiltrates within these sites at 2 h postinoculation.
The reduced infiltration in calves with BLAD occurred despite the
presence of an extremely large number of neutrophils in peripheral
blood that is typical for these calves. The large number of neutrophils
in the blood of calves with BLAD is probably a physiologic response
that can occur without microbial colonization, since one calf with BLAD that was raised under germ-free conditions had large numbers of neutrophils in the blood that were similar to those in a calf with BLAD
that was raised conventionally. Neutrophil counts in the germ-free and
conventionally reared calves with BLAD were much higher than those in
the three normal calves raised under germ-free conditions. The work in
this study demonstrates that during the initial inflammatory response,
neutrophils with normal CD18 expression pass more readily than
CD18-deficient neutrophils into the walls and lumen of bronchi and
bronchioles. It suggests that CD18 is needed for initial passage
through the extensive extracellular matrix of the bronchi and
bronchioles. This has potential importance for the development of
therapies to direct or inhibit neutrophil infiltration into conducting
airways rather than alveolar spaces.
*
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 Public Health Sciences, Wake Forest
University Baptist Medical Center, Winston-Salem, NC 27157-1063.
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