Leukotoxin kills rodent WBC by targeting leukocyte function associated antigen 1

Kristina M. DiFranco, Rajesh H. Kaswala, Chandni Patel, Chinnaswam Kasinathan, Scott Kachlany

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Leukotoxin is a protein that is secreted by Aggregatibacter actinomycetemcomitans and that primarily targets the active form of leukocyte function associated antigen 1 (LFA1) on WBC. Because of its specificity for WBC, leukotoxin is being developed as a novel biologic treatment for hematologic malignancies and autoimmune-inflammatory diseases. Early studies indicated that leukotoxin is specific for WBC from humans and Old World primates. In the current study, we used in vivo and in vitro assays to show that leukotoxin has a wider host range than previously believed and can kill rodent WBC. Administration of leukotoxin to rats and mice resulted in a rapid drop in WBC number but had no effect on RBC or platelet counts. Using LFA1-knockout mice, we showed that leukotoxin-mediated depletion of WBC is dependent on LFA1. In addition, similar to its effect on human monocytes, leukotoxin kills murine myeloid leukemia via a lysosome-mediated pathway that is dependent on cathepsin D. This newly described broader host range of leukotoxin enables the biology of the protein to be studied in rodent species and offers the possibility of using rodent models for evaluating the therapeutic efficacy of leukotoxin in various diseases.

Original languageEnglish (US)
Pages (from-to)331-337
Number of pages7
JournalComparative Medicine
Volume63
Issue number4
StatePublished - Aug 1 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • veterinary(all)

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