1. Academic Validation
  2. Differences in Staining for Neutrophil Elastase and its Controlling Inhibitor SLPI Reveal Heterogeneity among Neutrophils in Psoriasis

Differences in Staining for Neutrophil Elastase and its Controlling Inhibitor SLPI Reveal Heterogeneity among Neutrophils in Psoriasis

  • J Invest Dermatol. 2020 Jul;140(7):1371-1378.e3. doi: 10.1016/j.jid.2019.12.015.
Joanna Skrzeczynska-Moncznik 1 Katarzyna Zabieglo 1 Oktawia Osiecka 1 Agnieszka Morytko 1 Piotr Brzoza 1 Lukasz Drozdz 1 Monika Kapinska-Mrowiecka 2 Brice Korkmaz 3 Maciej Pastuszczak 4 Joanna Kosalka-Wegiel 5 Jacek Musial 5 Joanna Cichy 6
Affiliations

Affiliations

  • 1 Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
  • 2 Department of Dermatology, Zeromski Hospital, Kraków, Poland.
  • 3 INSERM (National Institute for Medical Research) U-1100, "The Research Center for Respiratory Diseases" and The University of Tours, Tours, France.
  • 4 Department of Dermatology, Jagiellonian University Medical College, Kraków, Poland; Department of Medicine, Jagiellonian University Medical College, Kraków, Poland.
  • 5 Department of Medicine, Jagiellonian University Medical College, Kraków, Poland.
  • 6 Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland. Electronic address: [email protected].
Abstract

Neutrophils are broadly classified into conventional neutrophils (PMNs) and low-density granulocytes (LDGs). LDGs are better than PMNs at generating neutrophil extracellular traps (NETs), which may contribute to the pathology of autoimmune diseases. We hypothesized that LDGs and PMNs differ in their levels of unrestrained NE that supports NET generation. Here, we show that individuals with psoriasis contain elevated levels of LDGs and that in contrast to PMNs, the LDGs display higher staining for NE and lower staining for its inhibitor SLPI. The heterogeneity between blood-derived LDGs and PMNs was somewhat reminiscent of the differences in the NE and SLPI staining patterns observed in psoriasis skin-infiltrating neutrophils. Distinctive staining for NE and SLPI in LDGs and PMNs did not result from differences in their protein levels nor manifested in higher total proteolytic activity of NE in LDGs; rather, it likely depended on different cytosolic sequestration of these proteins. The disparate profile of NE and SLPI in LDGs and PMNs coincided with altered migratory responses of these cells to cutaneous chemoattractants. Collectively, differential NE and SLPI staining identifies common attributes of both circulating and skin-infiltrating neutrophils, which may guide neutrophil migration to distinct skin regions and determine the localization of LDGs-mediated cutaneous pathology.

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