MASP-1 is crucial for lectin pathway activation in human serum, while neither MASP-1 nor MASP-3 are required for alternative pathway function

Immunobiology ◽  
2012 ◽  
Vol 217 (11) ◽  
pp. 1218-1219 ◽  
Author(s):  
Soren E. Degn ◽  
Lisbeth Jensen ◽  
Annette G. Hansen ◽  
Duygu Duman ◽  
Mustafa Tekin ◽  
...  
Keyword(s):  
Human Serum ◽  
Alternative Pathway ◽  
Lectin Pathway ◽  
Pathway Activation ◽  
Pathway Function

scholarly journals Complement 1 Inhibitor Is a Regulator of the Alternative Complement Pathway

2001 ◽  
Vol 194 (11) ◽  
pp. 1609-1616 ◽  
Author(s):  
Haixiang Jiang ◽  
Eric Wagner ◽  
Huamei Zhang ◽  
Michael M. Frank
Keyword(s):  
Human Serum ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Alternative Pathway ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Cobra Venom Factor ◽  
Factor B ◽  
Alternative Complement ◽  
Pathway Function ◽  
Cross Competition

We studied complement 1 inhibitor (C1-INH) as an inhibitor of the alternative complement pathway. C1-INH prevented lysis, induced by the alternative complement pathway, of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes in human serum. It inhibited the binding of both factors B and C3 to PNH and rabbit erythrocytes and blocked the ability of factor B to restore alternative-pathway function in factor B–depleted serum. C1-INH did not bind to factors B or D but did bind to immobilized C3b and cobra venom factor (CVF), a C3b analogue. C1-INH prevented factor B from binding to CVF-coated beads and dissociated bound factor B from such beads. Factor B and C1-INH showed cross competition in binding to CVF-coated beads. Factor D cleaved factor B into Bb and Ba in the presence of C3b. Cleavage was markedly inhibited when C3b was preincubated with C1-INH. C1-INH inhibited the formation of CVFBb and decreased the C3 cleavage. Removal of C1-INH from serum, in the presence of Mg-EGTA with an anti–C1-INH immunoabsorbant, markedly increased alternative-pathway lysis. C1-INH interacts with C3b to inhibit binding of factor B to C3b. At physiologic concentrations, it is a downregulator of the alternative pathway convertase.

Quantitative characterization of the autoactivation steps of MASP-1 and -2: Toward a kinetic model of lectin pathway activation

2011 ◽  
Vol 48 (14) ◽  
pp. 1668-1669
Author(s):  
J. Dobó ◽  
M. Megyeri ◽  
K. Szilágyi ◽  
V. Harmat ◽  
P. Závodszky ◽  
...  
Keyword(s):  
Kinetic Model ◽  
Lectin Pathway ◽  
Quantitative Characterization ◽  
Pathway Activation

Acylation of the lipid a region of a Klebsiella pneumoniae LPS controls the alternative pathway activation of human complement

1994 ◽  
Vol 31 (16) ◽  
pp. 1239-1246 ◽  
Author(s):  
Anne Mey ◽  
Denise Ponard ◽  
Maurice Colomb ◽  
Gerard Normier ◽  
Hans Binz ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Lipid A ◽  
Alternative Pathway ◽  
Human Complement ◽  
Pathway Activation

scholarly journals Deposition of C3b and iC3b onto particulate activators of the human complement system. Quantitation with monoclonal antibodies to human C3.

1985 ◽  
Vol 161 (6) ◽  
pp. 1414-1431 ◽  
Author(s):  
S L Newman ◽  
L K Mikus
Keyword(s):  
Monoclonal Antibodies ◽  
Serum Concentration ◽  
Human Serum ◽  
Molecular Form ◽  
Alternative Pathway ◽  
Classical Pathway ◽  
Sds Page ◽  
Predominant Form ◽  
Hemophilus Influenzae Type B ◽  
Type 3

Monoclonal antibodies were used to determine the number and molecular form of C3 bound to particulate activators of the complement (C) system by human serum. Sheep erythrocytes (E) coated with IgM (EIgM) and IgG (EIgG) were used to study activation of the classical pathway (CP). Yeast (Y), rabbit erythrocytes (ER), and five species of bacteria (Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae type 3, Streptococcus pyogenes, and Hemophilus influenzae type b) were used to study activation of the alternative pathway (AP). The deposition of C3b onto EIgM and EIgG incubated in C7-deficient human serum was dependent on the serum concentration. At all serum concentrations tested, there was complete conversion of C3b to iC3b. Kinetic analysis of C3b deposition and conversion to iC3b indicated that these events occurred almost simultaneously; the reaction was completed by 15 min. The deposition of C3 onto the AP activators ER and Y was also dependent on serum concentration, and ER, but not Y, required the presence of Mg-EGTA and thus the activation of only the AP. C3b deposition and conversion to iC3b on Y was complete in 15 min, with 82% of bound C3 converted to iC3b. For ER, maximum C3 deposition required 30 min in both the presence and absence of Mg-EGTA. However, after 1 h of incubation, 74% of bound C2 was iC3b in the absence of Mg-EGTA, compared with only 52% in the presence of Mg-EGTA. Thus, even on AP activators, a large portion of C3b may be converted to iC3b, and this conversion is probably controlled by elements on the particle's surface. Studies with the five species of bacteria yielded similar results. Approximately 3-5 X 10(4) molecules of C3 were bound per microorganism, with opsonization being completed in 30 min. Remarkably, only 16-28% of bound C3 was in the form of iC3b, even after 2 h of incubation. The presence or absence of Mg-EGTA, or the addition of purified CR1 to the reaction mixture, did not significantly effect the ratio of C3b to iC3b. Finally, SDS-PAGE and autoradiography of particle-bound 125I-C3 fragments confirmed that there was no conversion of iC3b to C3d,g or C3d. The data obtained about the opsonization of bacteria suggest that the predominant form of C3 that is encountered by inflammatory phagocytes may be C3b.

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