The alpha-1 acid glycoprotein (orosomucoid; AAG) is a normal constituent of human plasma (650+/-215 microgram ml(-1)) which increases in concentration as much as fivefold in associations with acute inflammation and cancer, and thus is recognized as an acute phase protein. AAG consists of a single polypeptide chain, has a molecular weight of 44,100, and contains approximately 45% carbohydrate including 12% sialic acid; it is the most negatively charged of the plasma proteins. Certain of the biological properties of AAG are related to its sialic acid content; thus, clearance and immunogenicity of AAG are markedly increased on desialisation. The biological functions of AAG are largely unknown. AAG has the ability to inhibit certain lymphocyte re-activities including blastogenesis in response to concanavalin A, phytohaemagglutinin and allogeneic cells, and these inhibitory effects are enhanced in association with desialisation. In view of these observations, a report that unphysiologically large (5--15 mg ml(-1)) amounts of AAG inhibit the platelet aggregation induced by ADP and adrenaline, and evidence that a sialic acid-deficient species of AAG appears elevated in several chronic disease states, we compared the effects of AAG and its desialised counterpart (AAG-D) on platelet aggregation. We report that desialisation of AAG is associated with increased expression of activity inhibitory to the platelet aggregation otherwise observed on stimulation with ADP, collagen or thrombin.

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.

A glycerol lipoteichoic acid antigen from Streptococcus pyogenes 1-RP41 was found by rabbit erythrocyte hemolytic assay to activate the alternative complement pathway in human sera. Over a narrow concentration range of the teichoic acid, complement consumption was dose dependent, whereas at higher concentrations of the acid complement consumption could not be detected.

New Zealand white rabbits were administered soluble lipoteichoic acid from Streptococcuspyogenes 1-RP41 on alternate days for up to 30 days. An increased incidence of renal cortico-medullary calculi was observed after day 21; the use of fluorescent-labeled anti-teichoic acid antibody located teichoic acid predominantly in the cortical-associated tubules.