An Alternate Complement Pathway: C-3 Cleaving Activity, Not Due to [unk], on Endotoxic Lipopolysaccharide after Treatment with Guinea Pig Serum; Relation to Properdin

Abstract

The reaction between endotoxic lipopolysaccharide (LPS) and the guinea pig complement system was shown to proceed by way of an intermediate complex, LPS-X, which contains at least six guinea pig serum proteins. LPS-X, like EAC4,2a (sheep erythrocytes carrying antibody molecules and C4,2a complexes), destroys the C3 molecule by cleavage. On incubation at 370C, LPS-X loses its capacity to destroy C3 at about the same rate as the decay of EAC4,2a, so that it has been assumed that LPS-X carries C4,2a sites that are responsible for the destruction of C3.We have now shown that monospecific rabbit antiguinea pig C2, which effectively inhibits C3 cleavage by EAC4,2a, does not interfere with the destruction of C3 by LPS-X. Furthermore, not more than a trace of C2ad is released from LPS-X on incubation at 370C. These results indicate that LPS-X does not carry a significant quantity of C4,2a and, hence, that its capacity to destroy C3 is due to another factor which is presumably a component of the properdin system.On incubation of endotoxic lipopolysaccharide (LPS) from Gram-negative bacteria with guinea pig serum there occurs a complement fixation process which is unusual in that the late-acting complement (C) components C3, C5, C6, C7, C8, and C9 are destroyed, while the early-acting components Cl, C4, and C2 are not affected significantly (1). For this Abbreviations: C, C1, C2, C3, etc.: C refers to complement, and the numbers indicate the components of the C system._The letter "a,"Y as in C2a, refers to a fragment. The "bar" in C1, or C4,2a, indicates an enzymically active component or complex. Nomenclature of Bull. Wld. Hlh. Org., 39, 935 (1968 reason it has been proposed that the reaction between LPS and the C system follows an alternate pathway in which the early-acting C components are bypassed. Similar observations were made about two decades ago by Pillemer and associates (2) in studies of the reaction between zymosan, an insoluble carbohydrate from the cell wall of yeast, and the C system. These investigators also considered a kind of alternate pathway involving a previously unrecognized serum protein, which they named properdin.Studies (3) have shown that LPS does not react directly with C3 or with the other late-acting C components but proceeds by way of an intermediate, LPS-X, which is formed on brief incubation of LPS with guinea pig serum at 370C, and which comprises at least six guinea pig serum proteins, including gamma globulin and C3. LPS-X, unlike LPS, reacts directly with C3, destroying it by cleavage. LPS-X resembles the intermediate EAC4,2a (sheep erythrocytes carrying antibody molecules and C4,2a complexes), which cleaves C3 directly. Moreover, on incubation at 370C LPS-X loses its ability to destroy C3 at about the same rate as the decay of EAC4,2a. For these reasons, it has been proposed that LPS-X may carry C4,2a sites and that these are responsible for its ability to destroy C3. However, some have thought that this interpretation is at odds with the fact that the early-acting C componen...

ANTICOMPLEMENTARY ACTIVITY AND COMPLETE 13C NMR ASSIGNMENT OF CITROSTADIENOL FROM SCHIZANDRA CHINENSIS

“…2). The IC so was 4.6 x 10-8 M. This result showed that its activity was much higher than those of lipopolysaccharide (Gewurz et al, 1968: Marcus et al, 1971, 6-branched,~(l~3)glucan (Hamuro et al, 1978), arabinan -…”

“…The activation of complement releases C3 a , C4 a , and C5 a , but they result in organ transplant rejection (Miyagawa et al, 1988;Dimond, 1995), asthma, allergy, atopys dermatitis (Groggel et al, 1983;Rother et al, 1985;Strunk et al, 1988;Alexandef et al, 1988;McGeer and McGeer, 1995), arthritis, systemic lupus erythematosus and ARDS (Carson, 1985;Murry et al, 1988;Zvaifler, 1989). For the prevention and treatment of these diseases, anticomplementary polysaccharides, for example, lipopolysaccharide (Gewurz et al, 1968;Marcus et al, 1971), 6-* Author to whom correspondence should be addressed. Muller-Eberhard, 1971) have already been isolated from bacteria, fungi and plants.…”

C1r deficiency: an inborn error associated with cutaneous and renal disease

“…Recently it has been emphasized that the complement system can be activated by alternate pathways (21)(22)(23)(24). Sera deficient in Clr provided a useful new reagent with which to study the concept of the alternate pathways.…”

Escherichia Coli Bacteremia in the Squirrel Monkey I. EFFECT OF COBRA VENOM FACTOR TREATMENT

“…Electron micrographs of gram-negative bacteria after incubation with antibody and complement demonstrate the development of circumscribed defects in the bacterial cell walls (1,2). The in vitro incubation of endotoxin with a variety of animal sera results in the inactivation of selected complement components with the generation of complement-derived chemotactic and anaphylatoxic factors (3)(4)(5)(6)(7)(8)(9)(10)(11)(12) Received for publication 9 June 1972 and in revised form 10 October 1972.…”