C-reactive protein and the acute phase response.
Since its discovery approximately fifty years ago, CRP has been recognized as the prototype acute phase reactant. Now appreciated as a trace serum protein that elevates markedly in concentration in association with inflammation and tissue necrosis, CRP also has been found deposited at sites of cell injury. Together with its long appreciated ability to initiate precipitation, agglutination, and capsular swelling reactions, these considerations early led to the surmise that CRP may play a role in the host adaptive response. Studies of its binding specificities have indicated that CRP has reactivity with (a) phosphocholine and phosphate esters, and hence with lipids widely distributed in mammalian and microbial cells; and (b) with multiple widely distributed polycations, including those derived from leukocyte granules. Interaction with either of these ligands has been shown to alter CRP in such a way that it can bring about activation of the complement system with generation of all the known C-dependent reactivities, including component consumption, adherence, phagocytosis, and cytolysis. Similarly, modified CRP has been shown to react with the FcR or a closely related receptor of monocytes and lead to phagocytosis, to react with certain FcR-bearing lymphocytes, and to activate the platelet. Thus, CRP shares with immunoglobulins the ability to initiate multiple effector functions that have been associated with the inflammatory response, as well as to bring about primary recognition reactions. Obviously CRP-ligand reactions would be favored during intervals of acute inflammation and tissue necrosis, when larger amounts of CRP are available. Therefore, in addition to serving as a diagnostic aid for the presence of inflammatory and necrotic processes, elevated levels of CRP may well provide an important component of the nonspecific host mechanisms, particularly in the early stages following inflammatory stimuli. Inquiries into the structure and function of CRP indicated an unexpected relationship of this molecule to an amyloid-related protein. The amyloid P component shows remarkable structural similarity to CRP and also exhibits calcium-dependent reactivity with widely distributed ligands; those appreciated to date have mainly involved polysaccharides derived from fungi and natural products. While the only relationship of SAP to an immune-related effector system found to date is reactivity with altered C3, it nonetheless seems plausible that SAP, which like CRP recognizes certain microbial and altered host molecules and has the potential of activating a host effector system at the recognition site. Further inquiry into the structure and functional relationships of these molecules, which are broadly distributed through the vertebrates, should help to reveal the role that CRP and other acute phase proteins have in the body economy and provide additional insights to the understanding of body defense mechanisms in inflammatory, repair, and defense processes generally.
D000208:Acute Disease; D000328:Adult; D000682:Amyloid / Q000276:immunology; D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007231:Infant, Newborn; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D009336:Necrosis; D011817:Rabbits; D000685:Serum Amyloid A Protein / Q000276:immunology; D000683:Serum Amyloid P-Component
D000682:Amyloid; D000685:Serum Amyloid A Protein; D000683:Serum Amyloid P-Component; D003165:Complement System Proteins; D002097:C-Reactive Protein