Sulfur mustard primes phagocytosis and degranulation in human polymorphonuclear leukocytes

Ashley K. Vavra, Cecilia J. Laurent, Vinh Ngo, John F. Sweeney, Jonathan M. Levitt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Sulfur mustard (2,2′-bis-chloroethyl-sulfide; SM) is a chemical warfare vesicant that causes debilitating skin lesions. Although a great deal of work has focused on the direct effects of SM exposure on the epithelium, it is unclear how much the inflammatory response, induced by exposure, contributes to lesion pathogenesis. Keratinocytes exposed to SM express a number of inflammatory mediators and elicit a cellular infiltrate consisting largely of polymorphonuclear leukocytes (PMN). PMN infiltration into SM lesions occurs as early as 30 min and peaks after several hours postexposure, and, despite the relatively short half-life of SM, PMN infiltrating a lesion could be exposed to micromolar concentrations of the agent. Previously, we have shown that exposure to low doses of sulfur mustard prime oxidative function in human PMN. The current study was undertaken to evaluate the effects of low-dose SM exposure on PMN phagocytosis, degranualtion and chemotaxis. PMN exposed to low doses of SM (50-200 μM) showed a dose-dependent enhancement of phagocytic function. Exocytosis of PMN azurophilic and specific granules [determined by analysis of granule-specific intravesicular receptors, Interleukin 10 receptor (IL-10R) and CD63] was also enhanced by SM exposure. Finally, we examined the effect of SM as a chemoattractant for PMN and show that SM is not itself a chemotaxin. These results suggest that SM injury may, in part, be caused by normal inflammatory function, and that therapeutic strategies aimed at down-regulating PMN activation could lessen the severity of SM injury and the time required for its resolution.

Original languageEnglish (US)
Pages (from-to)437-445
Number of pages9
JournalInternational Immunopharmacology
Volume4
Issue number3
DOIs
StatePublished - Mar 1 2004

Keywords

  • Apoptosis
  • Inflammation
  • Neutrophil
  • Priming
  • Sulfur mustard

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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