Impact of the GK-1 adjuvant on peritoneal macrophages gene expression and phagocytosis

Immunol Lett. 2018 Sep:201:20-30. doi: 10.1016/j.imlet.2018.10.010. Epub 2018 Nov 14.

Abstract

Purpose: The synthetic peptide GK-1 potentiates protective immunity elicited by the influenza vaccine in mice. In order to understand its adjuvant properties, this study was designed to determine the impact of GK-1 on gene expression and phagocytosis of peritoneal macrophages (PMa).

Methods: Increased gene expression of chemokines involved in leukocyte recruitment and of pro-inflammatory mediators was detected by microarray analysis of control and GK-1 treated PMa macrophages. The expression profile was subsequently confirmed by Multiplex Immunoassays analysis to measure cytokines levels, flow cytometer to describe M1/M2 surface markers and an assay to evaluate their phagocytic activity.

Results: Treatment of PMa with GK-1 results in development to the classically activated M1 functional macrophage subpopulation with increased expression of the CCL3 and CXCLO2 chemokines, IL-6 and TNF-α proinflammatory cytokines with a concomitant increase in the levels of NO, accompanied by the expression of modulatory factors that downregulate the inflammatory phenotype. GK-1 treated PMa significantly increased their phagocytic activity.

Conclusion: GK-1 classical activated with enhanced phagocitic capacity may underlie in the increased specific immunity induced when concomitant administered with other antigens.

Keywords: Adjuvant; GK-1; Gene expression; Macrophages; Phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / metabolism*
  • Animals
  • Cells, Cultured
  • Chemokine CCL3 / genetics
  • Female
  • Gene Expression Regulation
  • Immunity, Innate
  • Immunization
  • Interleukin-6 / genetics
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Peptides, Cyclic / metabolism*
  • Phagocytosis
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Adjuvants, Immunologic
  • Chemokine CCL3
  • Interleukin-6
  • Peptides, Cyclic
  • Tumor Necrosis Factor-alpha
  • cyclo(cysteinyl-glycyl-aspargyl-seryl-aspargyl-prolyl-lysyl-seryl-cysteine)