loading page

TSLP mediates bidirectional interactions between human lung macrophages and mast cells
  • +10
  • Gilda Varricchi,
  • Luisa Canè,
  • Remo Poto,
  • Francesco Palestra,
  • Ilaria Iacobucci,
  • Marinella Pirozzi,
  • Seetharaman Parashuraman,
  • Antonello La Rocca,
  • Edoardo Mercadante,
  • Piero Pucci,
  • Gianni Marone,
  • Stefania Loffredo,
  • Maria Monti
Gilda Varricchi
Universita degli Studi di Napoli Federico II Dipartimento di Scienze Mediche Traslazionali

Corresponding Author:[email protected]

Author Profile
Luisa Canè
Universita degli Studi di Napoli Federico II Dipartimento di Scienze Mediche Traslazionali
Author Profile
Remo Poto
Universita degli Studi di Napoli Federico II Dipartimento di Scienze Mediche Traslazionali
Author Profile
Francesco Palestra
Universita degli Studi di Napoli Federico II Dipartimento di Scienze Mediche Traslazionali
Author Profile
Ilaria Iacobucci
CEINGE Biotecnologie Avanzate sc a rl
Author Profile
Marinella Pirozzi
National Research Council (CNR
Author Profile
Seetharaman Parashuraman
National Research Council (CNR
Author Profile
Antonello La Rocca
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Author Profile
Edoardo Mercadante
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Author Profile
Piero Pucci
CEINGE Biotecnologie Avanzate sc a rl
Author Profile
Gianni Marone
Universita degli Studi di Napoli Federico II Dipartimento di Scienze Mediche Traslazionali
Author Profile
Stefania Loffredo
Universita degli Studi di Napoli Federico II Dipartimento di Scienze Mediche Traslazionali
Author Profile
Maria Monti
CEINGE Biotecnologie Avanzate sc a rl
Author Profile

Abstract

Background Thymic stromal lymphopoietin (TSLP), a pleiotropic cytokine mainly expressed by epithelial cells, plays a key role in asthma pathobiology. In humans, TSLP exists in two variants: the long form TSLP (lfTSLP) and a shorter TSLP isoform (sfTSLP), overlapping the lfTSLP C-terminus. Macrophages (HLMs) and mast cells (HLMCs) are in close proximity in the human lung and play central roles in different asthma phenotypes. Methods Immunofluorescence and Western blot were employed to localize intracellular TSLP. Limited proteolysis and mass spectrometry allowed the identification of cleavage sites of TSLP caused by tryptase and chymase. ELISA assays were employed to measure TSLP and VEGF-A. Results TSLP was detected in highly purified (≥ 99%) macrophages isolated from human lung and subcellularly localized in the cytoplasm by confocal microscopy and Western blot. IL-4 and lipopolysaccharide induced the release of TSLP from HLMs. HLMCs contain and release tryptase and chymase that specifically cleaved TSLP. Mass spectrometric analyses of TSLP treated with tryptase showed the production of 1-97 and 98-132 fragments. Chymase treatment of TSLP generated two peptides 1-36 and 37-132. HLM activation by lfTSLP induced VEGF-A, the most potent angiogenic factor, release. The four TSLP fragments generated by tryptase and chymase failed to activate HLMs. sfTSLP neither activated HLMs nor interfered with activating property of lfTSLP on HLMs. Conclusions Given the close proximity between mast cells and macrophages in the human lung, our results illuminate a new circuit between HLMs and mast cells. These findings have potential relevance in understanding novel aspects of asthma pathobiology.
25 Jun 2023Submitted to Allergy
25 Jun 2023Submission Checks Completed
25 Jun 2023Assigned to Editor
25 Jun 2023Review(s) Completed, Editorial Evaluation Pending
28 Jun 2023Reviewer(s) Assigned
03 Aug 2023Editorial Decision: Revise Minor