Activation of C3 and C5 May Be Involved in the Inflammatory Progression of PCM and GM

Abstract

Plasma cell mastitis (PCM) and granulomatous mastitis (GM) are the most common inflammatory diseases constituting nonbacterial mastitis (NBM). However, the pathogenesis of NBM remains unclear. In this study, risk factors for NBM were assessed, as well as the pathological features of PCM and GM. The levels of C3/C3a-C3aR and C5/C5a-C5aR1 of tissues were detected by IHC and WB. Exosomes were isolated from serum and identified by transmission electron microscopy. Then, C3 and C5 levels were detected in peripheral blood, and exosomes were assessed by flow cytometry and immunoelectron microscopy. Obesity and prolonged lactation were risk factors for NBM. The infiltration of plasma cells and lymphocytes around the dilated catheter in PCM and the formation of granulomatous structures in GM were the respective pathological features. C3/C3a-C3aR and C5/C5a-C5aR1 levels were elevated in PCM and GM tissue samples. There were no differences in peripheral blood levels of C3 and C5, while C3a and C5a were highly expressed in exosomes. These results suggest that the complement family is activated in PCM and GM, exosomes enrich C3a and C5a, and mediate the spread of inflammation. These findings provide new insights into the molecular mechanisms of PCM and GM and identify therapeutic targets.

Keywords: C3/C3a-C3aR; C5/C5a-C5aR1.; granulomatous mastitis; plasma cell mastitis.