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PMID: 8698496 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Pasteurella haemolytica leukotoxin induces bovine leukocytes to undergo morphologic changes consistent with apoptosis in vitro.

Infection and immunity ·Vol. 64 ·No. 7 ·1996-07-00 ·Pages 2687-94

Stevens PK, Czuprynski CJ

Abstract

Infection of the bovine lung with Pasteurella haemolytica results in an acute respiratory disorder known as pneumonic pasteurellosis. One of the key virulence determinants used by this bacterium is secretion of an exotoxin that is specific for ruminant leukocytes (leukotoxin). At low concentrations, the leukotoxin can activate ruminant leukocytes, whereas at higher concentrations, it inhibits leukocyte functions and is cytolytic, presumably as a result of pore formation and subsequent membrane permeabilization. We have investigated the possibility that the activation-inhibition paradox is explained in part by leukotoxin-mediated apoptosis (i.e., activation-induced cell death) of bovine leukocytes. Incubation of bovine leukocytes with P. haemolytica leukotoxin caused marked cytoplasmic membrane blebbing (zeiosis) and chromatin condensation and margination, both of which are hallmarks of apoptosis. The observed morphologic changes in bovine leukocytes were leukotoxin dependent, because they were significantly diminished in the presence of an anti-leukotoxin monoclonal antibody. In addition, bovine leukocytes incubated with culture supernatant from a mutant strain of P. haemolytica that does not produce any detectable leukotoxin failed to exhibit the morphologic changes characteristic of cells undergoing apoptosis. These observations may represent an important mechanism by which P. haemolytica overwhelms host defenses, contributing to the fibrinous pleuropneumonia characteristic of bovine pasteurellosis.

MeSH Terms
Adrenergic beta-Antagonists/pharmacology Animals Antibodies, Monoclonal/pharmacology Apoptosis Bacterial Toxins/antagonists & inhibitors,toxicity Calcium Channel Blockers/pharmacology Cattle Cell Membrane/drug effects,pathology Cell Nucleus/drug effects,pathology Cytotoxins/antagonists & inhibitors,toxicity Exotoxins/antagonists & inhibitors,toxicity In Vitro Techniques Leukocytes/drug effects,pathology Mannheimia haemolytica/genetics,pathogenicity Mutation Neutrophils/drug effects,pathology Pasteurellosis, Pneumonic/etiology,pathology Propranolol/pharmacology Verapamil/pharmacology
Chemicals
Adrenergic beta-Antagonists Antibodies, Monoclonal Bacterial Toxins Calcium Channel Blockers Cytotoxins Exotoxins leukotoxin Propranolol Verapamil
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Stevens P K
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison 53706, USA.
Czuprynski C J
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/iai.64.7.2687-2694.1996
Published
1996-07-00
Pages
2687-94
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC174127
Subset
IM
External Links
PubMed source DOI: 10.1128/iai.64.7.2687-2694.1996 PMC Full Text View journal details
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