title: Complement activation occurs through both classical and alternative pathways prior to onset and resolution of adult respiratory distress syndrome.
abstract: We have previously reported that plasma concentrations of the terminal complement (C) complex (TCC), C5b-9, increased significantly 2 days prior to onset of adult respiratory distress syndrome (ARDS) and also 1 day preceding its resolution. To determine the pathway of complement activation that preceded development and resolution of this acute inflammatory lung injury in septic patients, we quantified the C1rC1s-C1 inhibitor complex and the C3bP complex, which are generated following activation of classical and alternative complement pathways, respectively. Two days prior to diagnosis of ARDS, the plasma C1rC1s-C1 inhibitor complex and C3bP complex levels increased 22 and 14%, respectively. Furthermore, significant correlations were identified between concentrations of the TCC and C1rC1s-C1 inhibitor complex (r = 0.73, P = 0.003) and also with the levels of the TCC and C3bP complex (r = 0.81, P = 0.002) before onset of ARDS. Equally of interest, the C1rC1s-C1 inhibitor complex and C3bP complex concentrations increased 68 and 35%, respectively, 1 day before resolution of ARDS. Similarly, significant elevations of TCC concentrations preceding resolution of ARDS correlated with C1rC1s-C1 inhibitor complex (r = 0.66, P = 0.02) and also with C3bP complex (r = 0.72, P = 0.002) levels. Our results indicate that both the classical and alternative complement pathways are activated prior to onset of ARDS and also before its resolution in septic patients.
authors.affiliation: Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
authors.forename: P F
authors.initials: PF
authors.lastname: Langlois
authors.forename: M S
authors.initials: MS
authors.lastname: Gawryl
mesh_terms: D003166:Complement Activating Enzymes / Q000378:metabolism; D003167:Complement Activation; D003172:Complement C1 / Q000378:metabolism; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism; D015923:Complement C1r; D003173:Complement C1s / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D006801:Humans; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000276:immunology*; D018805:Sepsis / Q000150:complications / Q000276:immunology; D013997:Time Factors
chemical_list: D003172:Complement C1; D003174:Complement C1 Inactivator Proteins; D003179:Complement C3b; D003166:Complement Activating Enzymes; D015923:Complement C1r; D003173:Complement C1s; D011415:Complement Factor B