A HYPOTHESIS RESOLVING THE APPARENTLY DISPARATE ACTIVITIES OF NATIVE AND ALTERED FORMS OF HUMAN C-REACTIVE PROTEIN

Although C-reactive protein (CRP) has been studied for over 60 years, the in vivo function of this acute-phase reactant has not been clearly defined. The literature on CRP has been divided here into three categ ories: the cyclic, pentameric blood-borne form of CRP termed 'native' CRP which has activities mainly associated with the resolution of infl ammation, conformationally altered and aggregated forms of CRP which d isplay pro-inflammatory properties, and proteolytic forms of CRP exhib iting mixed activities. Since the activities of certain forms of CRP i n some cases contradict others, a hypothesis has been developed which reconciles these differences. It is proposed that distinct species of CRP are formed which have unique activities at an inflammatory site; c onformationally altered and proteolytic forms of CRP are created in su ccession from bound native CRP at the inflammatory site due to local c onditions (e.g. lowered pH, oxygen radicals, or possibly enzymes). Agg regated and/or conformationally altered forms of CRP initially promote inflammation, and subsequently produced peptide products either up or down regulate different leukocyte activities to aid in the progressio n of the inflammatory event. As the local conditions favoring the conv ersion of native CRP to altered forms begin to subside, native CRP the n predominates at the site, facilitating the removal of cellular debri s and resolution of the lesion.