Restriction of C1 hemolytic function by human proline-rich salivary proteins.
Acidic proline-rich salivary proteins, PRPI, PRPII, PRPIII, PRPIV, upper Db and Statherin, were isolated from parotid saliva and tested for interaction with complement. It was determined that each of the isolated proline-rich proteins blocked C1 hemolytic activity in assay systems where C1 was rate-limiting. Further studies comparing the specific activity of the proline-rich proteins to unfractionated parotid saliva indicated that other salivary substances (sensitive to urea treatment of parotid saliva) were also interacting with the first complement component but in a time-dependent manner. Based on a series of experiments examining the effect of the sequence of addition of the proline-rich proteins in the complement assay systems, it is postulated that these salivary proteins are able to block the proper interaction of C1 with EAC4 cells (sheep erythrocytes coated with antibody and C4gp). The proline-rich salivary proteins had no effect on C1 once C1 was bound to the immune complexes on the EAC4 cells. The C1 macromolecular complex undergoes conformational changes upon interaction with immune complexes resulting in a more avid binding of the C1q-Clr-Cls subunits with one another. Thus it is speculated that the EAC4-bound C1 becomes resistant to disruption by the proline-rich salivary proteins. Although the urea-sensitive factors had the highest specific C1-fixing activity, the activity of the acidic proline-rich proteins on C1 is important because of their relatively high concern in salivary secretions. Since complement-containing serous exudates and transudates are present on inflamed mucosal tissues, salivary substances which interact with C1 may play a role in regulating the initiation of the classical complement pathway, particularly at those mucosal sites where there is a high ratio of salivary secretion to serous exudate.
D002850:Chromatography, Gel; D003172:Complement C1 / Q000276:immunology; D003174:Complement C1 Inactivator Proteins; D004589:Electrophoresis, Disc; D004912:Erythrocytes / Q000276:immunology; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D010455:Peptides / Q000494:pharmacology*; D011392:Proline; D055232:Proline-Rich Protein Domains; D011489:Protein Denaturation; D012471:Salivary Proteins and Peptides / Q000494:pharmacology*; D014508:Urea
D003172:Complement C1; D003174:Complement C1 Inactivator Proteins; D010455:Peptides; D012471:Salivary Proteins and Peptides; D014508:Urea; D011392:Proline