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Infection and Immunity, January 2000, p. 72-79, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Lymphocyte Function-Associated Antigen 1 Is a
Receptor for Pasteurella haemolytica Leukotoxin in
Bovine Leukocytes
S.
Jeyaseelan,1
S. L.
Hsuan,1
M. S.
Kannan,1
B.
Walcheck,1
J. F.
Wang,2
M. E.
Kehrli,3
E. T.
Lally,2
G. C.
Sieck,4 and
S. K.
Maheswaran1,*
Department of Veterinary PathoBiology,
College of Veterinary Medicine, University of Minnesota, St. Paul,
Minnesota 551081; Leon Levy Research
Center for Oral Biology, University of Pennsylvania, Philadelphia,
Pennsylvania 191042; Metabolic Diseases
and Immunology Research Unit, National Animal Disease Center, Ames,
Iowa 500103; and Departments of
Anesthesiology and of Physiology and Biophysics, Mayo Clinic,
Rochester, Minnesota 559054
Received 13 August 1999/Returned for modification 4 October
1999/Accepted 14 October 1999
Pasteurella (Mannheimia) haemolytica leukotoxin (Lkt)
causes cell type- and species-specific effects in ruminant leukocytes. Recent studies indicate that P. haemolytica Lkt binds to
bovine CD18, the common subunit of all
2 integrins. We designed
experiments with the following objectives: to identify which member of
the
2 integrins is a receptor for Lkt; to determine whether Lkt
binding to the receptor is target cell (bovine leukocytes) specific; to define the relationships between Lkt binding to the receptor, calcium
elevation, and cytolysis; and to determine whether a correlation exists
between Lkt receptor expression and the magnitude of target cell
cytolysis. We compared Lkt-induced cytolysis in neutrophils from
control calves and from calves with bovine leukocyte adhesion deficiency (BLAD), because neutrophils from BLAD-homozygous calves exhibit reduced
2 integrin expression. The results demonstrate for
the first time that Lkt binds to bovine CD11a and CD18 (lymphocyte function-associated antigen 1 [LFA-1]). The binding was abolished by
anti-CD11a or anti-CD18 monoclonal antibody (MAb). Lkt-induced calcium
elevation in bovine alveolar macrophages (BAMs) was inhibited by
anti-CD11a or anti-CD18 MAb (65 to 94% and 37 to 98%, respectively, at 5 and 50 Lkt units per ml; P < 0.05). Lkt-induced
cytolysis in neutrophils and BAMs was also inhibited by anti-CD11a or
anti-CD18 MAb in a concentration-dependent manner. Lkt bound to porcine LFA-1 but did not induce calcium elevation or cytolysis. In neutrophils from BLAD calves, Lkt-induced cytolysis was decreased by 44% compared to that of neutrophils from control calves (P < 0.05). These results indicate that LFA-1 is a Lkt receptor, Lkt binding
to LFA-1 is not target cell specific, Lkt binding to bovine LFA-1
correlates with calcium elevation and cytolysis, and bovine LFA-1
expression correlates with the magnitude of Lkt-induced target cell cytolysis.
*
Corresponding author. Mailing address: Department of
Veterinary PathoBiology, University of Minnesota, 1971 Commonwealth
Ave., St. Paul, MN 55108. Phone: (612) 625-6264. Fax: (612) 624-4785. E-mail: mahes001{at}maroon.tc.umn.edu.
Infection and Immunity, January 2000, p. 72-79, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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