Stimulation of human neutrophils, monocytes, and platelets by modified C-reactive protein (CRP) expressing a neoantigenic specificity.
C-reactive protein (CRP) can be structurally modified by heat, acid, or urea-chelation to express a neoantigen designated by us as neo-CRP. This antigen is also expressed on the in vitro primary protein translation products of both human and rabbit CRP. Unmodified CRP and CRP complexed with pneumococcal C-polysaccharide (CPS) do not express neo-CRP. Forms of CRP expressing neo-CRP but not native CRP antigenicity (even in the presence of CPS) consistently and in a dose-dependent manner potentiated the respiratory burst response of human polymorphonuclear leukocytes and peripheral blood monocytes to heat-modified IgG. Forms of CRP expressing neo-CRP antigenicity also induced reactions of aggregation and secretion from isolated platelets and potentiated platelet activation stimulated by ADP in platelet-rich-plasma, while native CRP alone or complexed with CPS again did not. Unlike CRP-CPS complexes, forms of CRP expressing neo-CRP were not able to activate the complement system. These data emphasize the biologic potential inherent in this humoral acute-phase reactant, particularly in the activation of the formed elements of the blood important in the inflammatory response. Since these cell-activating properties are preferentially observed when CRP is structurally modified to express the neo-CRP antigen, such a molecular conversion may be central to the structure-function relationships of CRP at local sites of inflammation and tissue injury.
Potempa
L A
LA
Department of Immunology, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois.
Zeller
J M
JM
Fiedel
B A
BA
Kinoshita
C M
CM
Gewurz
H
H
D001792:Blood Platelets / Q000276:immunology*; D002097:C-Reactive Protein / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D009504:Neutrophils / Q000276:immunology*; D010974:Platelet Aggregation
D000939:Epitopes; D002097:C-Reactive Protein