Mannheimia haemolytica leukotoxin-induced cytolysis of ovine (Ovis aries) leukocytes is mediated by CD18, the beta subunit of beta2-integrins

Rohana P Dassanayake; Sudarvili Shanthalingam; William C Davis; Subramaniam Srikumaran

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Mannheimia haemolytica leukotoxin-induced cytolysis of ovine (Ovis aries) leukocytes is mediated by CD18, the beta subunit of beta2-integrins

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Mannheimia haemolytica leukotoxin-induced cytolysis of ovine (Ovis aries) leukocytes is mediated by CD18, the beta subunit of beta2-integrins

Rohana P Dassanayake, Sudarvili Shanthalingam, William C Davis and Subramaniam Srikumaran

Microbial pathogenesis, Vol.42(5-6), pp.167-173

05/2007

Handle:

https://hdl.handle.net/2376/110566

PMID: 17368825

Abstract

CD18 Antigens - immunology

Sheep, Domestic

Mannheimia haemolytica - pathogenicity

Pasteurellosis, Pneumonic - microbiology

Exotoxins - metabolism

Mastocytoma - genetics

Transfection

Leukocytes, Mononuclear - immunology

Pasteurellosis, Pneumonic - immunology

Neutrophils - microbiology

Antibodies, Monoclonal - immunology

Leukocytes, Mononuclear - microbiology

CD18 Antigens - genetics

Antibodies, Monoclonal - pharmacology

Bacterial Toxins - immunology

Exotoxins - immunology

Mannheimia haemolytica - metabolism

Neutrophils - immunology

Mannheimia haemolytica - immunology

Mastocytoma - microbiology

Pasteurellosis, Pneumonic - blood

CD18 Antigens - metabolism

Mastocytoma - immunology

Bacterial Toxins - metabolism

Animals

Cell Line, Tumor

Mice

CD18 Antigens - biosynthesis

Mannheimia (Pasteurella) haemolytica causes severe pneumonia in cattle, sheep and goats. Leukotoxin (Lkt) is the most important virulence determinant produced by this organism. Previously, we identified CD18, the beta subunit of beta(2)-integrins, as the receptor for Lkt on bovine leukocytes. Since Lkt is specific for leukocytes of cattle, sheep and goats, we hypothesized that Lkt utilizes CD18 as its receptor on ovine leukocytes as well. Therefore, the objective of this study was to transfect an Lkt-resistant murine cell line (P815) with cDNA encoding ovine CD18, and to determine the susceptibility of the transfectants to Lkt-induced cytolysis. cDNA for ovine CD18 cloned from polymorphonuclear leukocytes was transfected into P815 cells. Flow cytometric analysis of the transfectants revealed surface expression of ovine CD18, and Lkt binding. In a cytotoxicity assay, the transfectants were lysed by Lkt in a concentration-dependent manner, whereas the parent cells were not. Pre-incubation of Lkt with an anti-Lkt neutralizing antibody and pre-incubation of transfectants with an anti-CD18 antibody resulted in inhibition of cytolysis confirming the interaction between Lkt and CD18. Taken together, these results indicate that CD18 on ovine leukocytes serves as a receptor for Lkt, and that CD18 is sufficient to mediate Lkt-induced cytolysis of ovine leukocytes.

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Title: Mannheimia haemolytica leukotoxin-induced cytolysis of ovine (Ovis aries) leukocytes is mediated by CD18, the beta subunit of beta2-integrins
Creators: Rohana P Dassanayake - Department of Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA
Sudarvili Shanthalingam
William C Davis
Subramaniam Srikumaran
Publication Details: Microbial pathogenesis, Vol.42(5-6), pp.167-173
Academic Unit: Veterinary Microbiology and Pathology, Department of
Publisher: England
Identifiers: 99900547048801842
Language: English
Resource Type: Journal article

Mannheimia haemolytica leukotoxin-induced cytolysis of ovine (Ovis aries) leukocytes is mediated by CD18, the beta subunit of beta2-integrins

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