Increased soluble phagocytic receptors sMer, sTyro3 and sAxl and reduced phagocytosis in juvenile-onset systemic lupus erythematosus

Pediatr Rheumatol Online J. 2015 Apr 10;13:10. doi: 10.1186/s12969-015-0007-y. eCollection 2015.

Abstract

Background: The TAM-receptor tyrosine kinase family, Tyro3, Axl and Mer are key to apoptotic cell clearance. Reduced phagocytic clearance in systemic lupus erythematosus (SLE) leads to prolonged exposure of nuclear autoantigen to the immune system. Here we measure the levels of TAM receptors and the phagocytic capacity of monocytes and macrophages in juvenile-onset SLE (JSLE).

Method: Mer protein was measured on monocytes from JSLE, healthy control and JIA patients. JSLE, healthy control and JIA patients' plasma were analysed for soluble Mer (sMer), soluble Tyro3 (sTyro) and soluble Axl (sAxl). A phagocytosis assay measured the effect of JSLE serum on phagocytic potential of JSLE and control monocytes to engulf E. Coli bacteria and healthy macrophages to engulf apoptotic neutrophils.

Results: Mer receptor expression was significantly decreased on JSLE monocytes compared to healthy controls. Plasma sMer, sTyro and sAxl were significantly increased in JSLE patients compared to controls (p < 0.05). Adult healthy control macrophages had significantly decreased phagocytosis of E. Coli and apoptotic neutrophils in the presence of 10% JSLE serum compared to control serum (p < 0.05).

Conclusion: JSLE patients have a decreased phagocytosis due to both serum and cell-derived factors. Significantly increased levels of sMer, sTyro3 and sAxl may be important factors contributing to the deficit in phagocytosis ability.

Keywords: Juvenile-onset SLE; Phagocytosis; TAM receptor; apoptotic cell clearance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / metabolism
  • ADAM17 Protein
  • Adolescent
  • Age of Onset
  • Apoptosis / physiology
  • Arthritis, Juvenile / epidemiology
  • Arthritis, Juvenile / metabolism
  • Arthritis, Juvenile / physiopathology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Escherichia coli / metabolism
  • Female
  • Humans
  • Lupus Erythematosus, Systemic / epidemiology
  • Lupus Erythematosus, Systemic / metabolism*
  • Lupus Erythematosus, Systemic / physiopathology*
  • Male
  • Monocytes / metabolism
  • Monocytes / pathology
  • Neutrophils / pathology
  • Phagocytosis / physiology*
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Immunologic / metabolism*
  • c-Mer Tyrosine Kinase

Substances

  • Proto-Oncogene Proteins
  • Receptors, Immunologic
  • phagocytosis receptor
  • MERTK protein, human
  • Receptor Protein-Tyrosine Kinases
  • TYRO3 protein, human
  • axl receptor tyrosine kinase
  • c-Mer Tyrosine Kinase
  • ADAM Proteins
  • ADAM17 Protein