Immunohistochemical Staining Reveals C-Reactive Protein Existing Predominantly as Altered Conformation Forms in Inflammatory Lesions

C-reactive protein (CRP) is an established marker of inflammation and has been proposed to play a proinflammatory role in pathologies of several diseases. CRP is primarily produced by the liver and released into circulation as a pentameric molecule composed of five identical subunits. It has been suggested that the activation of the proinflammatory actions of CRP requires sequential conformational changes triggered by local inflammatory conditions. These include the dissociation into the subunit form (monomeric CRP, mCRP) and further reduction of the intra-subunit disulfide bond of mCRP. This model predicts that mCRP is the primary isoform present in inflamed but not healthy tissues, however the supporting evidence is lacking. Herein, we stained tissue samples across multiple anatomical locations from several types of human diseases with highly selective monoclonal antibodies that can differentiate CRP and mCRP. The results indicated that mCRP is the predominant form existing in the lesions. Further immunoblotting of the patient tissue samples revealed the potential presence of reduced mCRP. Together, we conclude that mCRP but not CRP is the major isoform present in local inflammatory lesions, supporting the so-called cascading model of CRP function and regulation.