MAC mediates mammary duct epithelial cell injury in plasma cell mastitis and granulomatous mastitis

Int Immunopharmacol. 2022 Dec;113(Pt A):109303. doi: 10.1016/j.intimp.2022.109303. Epub 2022 Oct 14.

Abstract

Plasma cell mastitis (PCM) and granulomatous mastitis (GM) are common inflammatory nonbacterial mastitis (NBM). However, the pathogenesis of NBM is still unclear.

Methods: In this study, we statistically analyzed the pathological features of PCM and GM using pathological HE staining and tissue transmission electron microscopy. The levels of MAC (C5b-9n), P-selectin, E-selectin, and ICAM-1 were detected through IHC, WB, ELISA, and qPCR. The expression level and location of MAC were observed by tissue immunological electron microscopy. In addition, exosomes were isolated from tissues, identified using transmission electron microscopy, and the densities were detected by Nano-FCM. Finally, the expression intensity of MAC in exosomes was detected by flow cytometry and immunoelectron microscopy.

Results: The damage and apoptosis of mammary duct epithelial cells are the common pathological features of PCM and GM. MAC is primarily located in the cell membrane of mammary ductal epithelial cells and is significantly expressed in PCM and GM. The density of exosomes in PCM and GM tissues was elevated, and MAC was highly expressed in exosomes. In addition, the expression of P-selectin, E-selectin, and ICAM-1 in PCM and GM was significantly higher than in the normal group.

Conclusion: We found severe damage of the mammary duct epithelial cells in PCM and GM tissues, which was verified by relevant pathological methods. Earlier studies demonstrated that MAC is highly expressed in PCM and GM tissues and exosomes seem to play a very important role in the understanding of MAC. Furthermore, MAC is involved in inflammatory infiltration and lesion of mammary duct epithelial cells upregulated by P-selectin, E-selectin, and ICAM-1. These findings provide new insights into PCM and GM molecular mechanisms.

Keywords: Granulomatous mastitis; Inflammation; MAC(C5b-9n); Plasma cell mastitis.

MeSH terms

  • Complement Membrane Attack Complex* / metabolism
  • E-Selectin / metabolism
  • Epithelial Cells / metabolism
  • Female
  • Granulomatous Mastitis* / metabolism
  • Granulomatous Mastitis* / pathology
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Mammary Glands, Human
  • Plasma Cells / metabolism

Substances

  • E-Selectin
  • Intercellular Adhesion Molecule-1
  • Complement Membrane Attack Complex