Molecular and biochemical mechanisms of Pasteurella haemolytica leukotoxin-induced cell death.

Abstract:

:Pasteurella haemolytica leukotoxin (LKT) is a member of the RTX family of pore-forming toxins that kill bovine immune cells. Several studies have suggested that RTX toxins kill target cells by the induction of apoptosis. In the present study, BL3 bovine leukaemia cells were exposed to LKT and assessed by molecular and flow cytometric techniques that measure different aspects of apoptotic cell death. The intoxicated cells demonstrated morphological, light scatter and Hoechst 33258 staining characteristics consistent with cells undergoing apoptosis. The cells also exhibited internucleosomal DNA fragmentation and poly (ADP-ribose) polymerase (PARP) cleavage, both indicators of apoptosis. LKT-treated cells bound annexin-V-FITC indicating that phosphatidylserine groups were translocated from the inner to the outer leaflet of the cell membrane. The effect of LKT on cells was dose dependent and inhibitable by incubation with anti-LKT monoclonal antibody. Finally, an early step for induction of apoptosis appears to be the binding of LKT to a beta2 integrin since pre-incubating cells with anti-beta2 integrin antibodies inhibited LKT-induced apoptosis. This study provides new insights into understanding the pathogenesis of bovine pasteurellosis and could lead to the development of both preventative and therapeutic strategies for disease management.

journal_name

Microb Pathog

journal_title

Microbial pathogenesis

authors

Wang JF,Kieba IR,Korostoff J,Guo TL,Yamaguchi N,Rozmiarek H,Billings PC,Shenker BJ,Lally ET

doi

10.1006/mpat.1998.0236

subject

Has Abstract

pub_date

1998-12-01 00:00:00

pages

317-31

issue

6

eissn

0882-4010

issn

1096-1208

pii

S0882-4010(98)90236-4

journal_volume

25

pub_type

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