Activation of platelets and the complement system in mice with Schistosoma-induced pulmonary hypertension

Am J Physiol Lung Cell Mol Physiol. 2024 Nov 1;327(5):L661-L668. doi: 10.1152/ajplung.00165.2024. Epub 2024 Sep 10.

Abstract

Schistosomiasis-induced pulmonary hypertension (PH) presents a significant global health burden, yet the underlying mechanisms remain poorly understood. Here, we investigate the involvement of platelets and the complement system in the initiation events leading to Schistosoma-induced PH. We demonstrate that Schistosoma exposure leads to thrombocytopenia, platelet accumulation in the lung, and platelet activation. In addition, we observed increased plasma complement anaphylatoxins C3a and C5a, indicative of complement system activation, and elevated platelet expression of C1q, C3, decay activating factor (DAF), and complement C3a and C5a receptors. Our findings suggest the active involvement of platelets in responding to complement system signals induced by Schistosoma exposure and form the basis for future mechanistic studies on how complement may regulate platelet activation and promote the development of Schistosoma-induced PH.NEW & NOTEWORTHY Schistosomiasis-induced pulmonary hypertension (PH) is a significant global health burden, yet the underlying mechanisms remain poorly understood. We demonstrate that Schistosoma exposure leads to platelet accumulation in the lung and platelet activation. We observed increased plasma levels of C3a and C5a, indicative of complement system activation, and elevated expression of platelet complement proteins and receptors. These findings underscore the role of platelets and complement in the inflammatory responses associated with Schistosoma-induced PH.

Keywords: Schistosoma; complement; inflammation; platelet; pulmonary hypertension.

MeSH terms

  • Animals
  • Blood Platelets* / immunology
  • Blood Platelets* / metabolism
  • Complement Activation
  • Complement C3a / metabolism
  • Complement C5a / metabolism
  • Complement System Proteins / metabolism
  • Female
  • Hypertension, Pulmonary* / etiology
  • Hypertension, Pulmonary* / immunology
  • Hypertension, Pulmonary* / metabolism
  • Hypertension, Pulmonary* / parasitology
  • Lung / immunology
  • Lung / metabolism
  • Lung / parasitology
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Platelet Activation*
  • Schistosoma / immunology
  • Schistosomiasis / complications
  • Schistosomiasis / immunology
  • Schistosomiasis / parasitology

Substances

  • Complement C3a
  • Complement System Proteins
  • Complement C5a