PubMed · 552284
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B D Williams. 1979. The complement system.. https://doi.org/10.1093/bja%2F51.1.7
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If a single component is lowered, it is reasonable to question whether the patient has a genetically-controlled defect. Studies of family members may be required. If split products, complexes, or neoantigens are present, it is likely that there is ongoing complement activation. If most of the components of a pathway are lowered, a reasonable supposition is that complement is being activated. We then turn to a consideration of the factors that may activate complement. When hypocomplementemia is associated with a decrease in titer of several components, it is often possible to determine whether the classic or alternative pathway is the major pathway being activated; this, in turn, may suggest certain diagnoses and rule out other diagnoses. The nature of the circulating complexes or split products may provide the same information. Thus, a consideration of the pathophysiology of the complement system and of the factors that activate complement provides an approach to an understanding of the function of complement and the role of complement causing a damage in a clinical setting.
The activation of human polymorphonuclear leukocytes (PMN) by particulate Tamm-Horsfall glycoprotein (THG) represents an interaction hitherto unrecognized. The potential pathophysiological effect of this phenomenon within the interstitium of the kidney is highlighted by the activation of the respiratory burst, as well as by comprehensive PMN degranulation. Products of the interaction are expressed in terms of phagocytosis, luminol-dependent chemiluminescence, granule marker enzyme release and arachidonic acid metabolism. Significant quantities of the primary, secondary and tertiary granule markers, myeloperoxidase, vitamin B12 binding protein and N-acetyl-beta-D-glucosaminidase, respectively, were secreted in a dose and time-dependent manner. Phagocytosis of the glycoprotein was accompanied by the generation of significant quantities of leukotriene B4. Furthermore, the ability of such a particulate ligand to activate the alternative pathway of complement clearly represents a capacity to augment the inflammatory response. Should the interaction of THG with PMN take place within the interstitium of the kidney, augmented by the deposition of complement proteins on the surface of insoluble aggregates, the resulting inflammatory response may lead to marked tissue damage and eventually result in interstitial fibrosis.
The trypsin-sensitive receptor that mediates phagocytosis of unopsonized zymosan particles by human monocytes has been designated as a beta-glucan receptor because of its functional inhibition by specific algal and plant beta-glucans. Soluble ligands that are chemically and structurally identical to beta-glucan constituents of zymosan were isolated from a carbohydrate-enriched fraction of yeast extract by sequential chromatography on DE-cellulose, SP-Sephadex, and Con A-Sepharose. Preincubation of adherent human monocytes with 278, 210, and 2.5 micrograms/ml hexose equivalents in pooled chromatographic fractions from DE-cellulose, SP-Sephadex, and Con A-Sepharose, respectively, effected 50% reductions in subsequent phagocytosis of zymosan particles without affecting Fc-mediated ingestion of IgG-coated sheep erythrocytes (ESIgG). The purified yeast extract-derived beta-glucans, which contained 92% glucose and 8% mannose by gas chromatographic analysis and eluted from a Sephacryl S-200 column as a broad peak with a Kav of 0.39 and estimated molecular sizes of from 20,000 to 70,000 m.w., required only 3.5 +/- 0.9 micrograms/ml (mean +/- SD, n = 6), as compared with 31.5 micrograms/ml of the algal beta-glucan laminarin to achieve 50% decreases in zymosan ingestion. Alternatively, soluble yeast beta-glucans with estimated molecular sizes of from 2 X 10(5) to 2 X 10(6) were prepared from yeast glucan particles, which contained 98% glucose and 0% mannose, by sonication and sequential centrifugation at 15,000 and 100,000 X G for 30 and 60 min, respectively. Monocyte ingestion of zymosan was reduced by 50% by pretreatment with 60 ng/ml of the soluble beta-glucans in 15,000 X G supernatants, whereas ingestion of ESIgG was unaffected by as much as 50 micrograms/ml of this material. Partial acid hydrolysis of soluble glucan-derived beta-glucans in 15,000 X G supernatants followed by gel filtration on Bio-Gel P-4 revealed two well-defined peaks within the inclusion volume of the column with phagocytosis-inhibiting activity. Oligoglucosides that eluted at a Kav of 0.46 had an estimated molecular size of 2,000 m.w. and effected a 48% reduction in zymosan ingestion at inputs of 2 to 5 micrograms/ml, and smaller oligoglucosides with a Kav of 0.82 and an estimated molecular size of 1,000 m.w. effected a 50% reduction at inputs of 25 micrograms/ml. Preincubation of monocytes for 2 min with 25 micrograms/ml of the oligoglucosides with estimated molecular size of 1,000 m.w. and with 50 ng/ml of soluble glucan-derived beta-glucans in 100,000 X G supernatants reduced zymosan ingestion by 41% +/- 4 and 44% +/- 3 (mean +/- SD, n = 3), respectively.(ABSTRACT TRUNCATED AT 400 WORDS)