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PubMed2003

Administration of a soluble recombinant complement C3 inhibitor protects against renal disease in MRL/lpr mice.

Complement receptor 1-related gene/protein y (Crry) in rodents is a potent membrane complement regulator that inhibits complement C3 activation by both classical and alternative pathways. To clarify the role of complement in lupus nephritis, MRL/lpr mice were given Crry as a recombinant protein (Crry-Ig) from 12 to 24 wk of age. Control groups were given saline or normal mouse IgG. Sera and urine were collected biweekly. Only 1 of 20 (5%) Crry-Ig-treated mice developed renal failure (BUN > 50 mg/dl) compared with 18 of 38 (47.4%) mice in control groups (P = 0.001). BUN levels at 24 wk were reduced from 68.8 +/- 9.7 mg/dl in control groups to 38.5 +/- 3.9 mg/dl in the Crry-Ig-treated group (P < 0.01). Urinary albumin excretion at 24 wk was also significantly reduced from 5.3 +/- 1.4 mg/mg creatinine in the control groups to 0.5 +/- 0.2 mg/mg creatinine in the Crry-Ig-treated group (P < 0.05). Of the histologic data at 24 wk, there was a significant reduction in scores for glomerulosclerosis and C3d, IgG, IgG3, and IgA staining intensity in glomeruli in complement-inhibited animals. Crry-Ig-treated animals were also protected from vasculitic lesions. Although there was no effect on relevant autoimmune manifestations such as anti-double stranded DNA titers or cryoglobulin IgG3 levels, circulating immune complex levels were markedly higher in complement-inhibited animals. Thus, inhibition of complement activation with Crry-Ig significantly reduces renal disease in MRL/lpr lupus mice. The data support the strategy of using recombinant complement C3 inhibitors to treat human lupus nephritis.

Albuminuria↗
PubMed2002

Bacterial expression and membrane targeting of the rat complement regulator Crry: a new model anticomplement therapeutic.

Inappropriate or unregulated activation of complement can contribute to pathology in inflammatory diseases. Previous studies have shown that soluble recombinant regulators of complement are effective in animal models and some human diseases. However, limitations include cost, rapid clearance, and unwanted systemic effects. To avoid some of these problems, bacterial expression of regulators has been optimized and methods for the addition of a membrane-targeting moiety to the complement regulator developed. When administered directly to sites of inflammation, membrane-targeted human regulators are retained and inhibit complement-activation locally. To test the efficacy of membrane-targeted complement regulators in vivo, we have undertaken the expression and membrane targeting of the rat-complement regulator Crry. A soluble recombinant form of Crry, containing only the first four short consensus repeats, was expressed in a mammalian expression system and shown to be functional as a fluid phase regulator. To generate the quantities required for testing in vivo, Crry was expressed in bacteria and refolded successfully. Refolded protein had full-complement regulatory activity in vitro. Attachment of a membrane address tag conferred membrane-binding capacity and greatly increased complement regulatory function in vitro. This novel anticomplement agent can now be applied to rat models of arthritis and other inflammatory diseases.

Animals↗
PubMed1986

Polymorphonuclear leukocytes, complement, and Trichophyton rubrum.

Trichophyton rubrum can activate complement. In order to assess the role of complement in host defense, fresh human serum was incubated with fungus. Factors were produced which were chemotactic for polymorphonuclear leukocytes (PMNL), but only if complement activation was allowed. This suggests that the chemotactic factor or factors were derived from complement. Incubation of T. rubrum with fresh serum did not prevent fungal growth on subsequent culture, but did inhibit incorporation of radiolabeled N-acetylglucosoamine. The interaction of PMNL and fungi was studied, and the role of complement as a mediator was assessed. PMNL adhered well to fungi provided that the fungal hyphae had been preincubated with fresh human serum to provide complement opsonins. Opsonized and unopsonized fungi both stimulated a respiratory burst in normal PMNL as measured by chemiluminescence, but the burst was generated much faster with opsonized hyphae. Although hyphae with adherent PMNL subsequently proliferated in culture, the incorporation of N-acetylglucosoamine was inhibited 96% when the hyphae were opsonized with fresh serum and then incubated with PMNL. Inhibition was also observed with unopsonized fungi, but to a lesser degree. Varying the ratio of PMNL to hyphae showed that inhibition by PMNL was far more efficient if hyphae were opsonized. In contrast to hyphae, opsonized fungal spores were killed by PMNL so that no growth was observed in subsequent cultures. This killing was not observed if PMNL were omitted or if spores were preincubated with heat-inactivated serum rather than fresh serum. Activation of complement apparently opsonizes the spores so that they can be ingested and killed by viable PMNL. Contents of disrupted PMNL failed to inhibit fungal growth. Complement and PMNL may aid the host in defending itself against infection by dermatophytes.

Acetylglucosamine↗
PubMed1982

Functional evidence for complement-activating immune complexes in the skin of patients with bullous pemphigoid.

Previous immunofluorescent studies showing deposits of immunoglobulin and complement at the cutaneous basement membrane zone have provided evidence supporting a role for immune complexes in the pathogenesis of bullous pemphigoid. In this study the functional activity of the deposits has been examined using leukocyte attachment, a method for detecting and quantitating the biological activity of complement-activating immune complexes in tissues. When peripheral blood leukocytes suspended in serum complement were incubated with cryostat sections of lesional and adjacent normal-appearing skin from 9 patients with pemphigoid, skin from 11 normal controls and lesional skin from 14 nonpemphigoid disease controls there was significantly greater attachment of leukocytes to the basement membrane zone of lesional bullous pemphigoid skin compared to normal-appearing pemphigoid skin and skin of both control groups. A significant reduction in attachment in the absence of serum complement suggested the reaction was dependent on activation of complement by tissue-deposited complexes. Although leukocyte attachment was greater in lesional than normal-appearing pemphigoid skin, a comparison of the incidence and intensity of cutaneous IgG and complement immunofluorescence between the 2 groups showed no significant differences. Furthermore, no correlation between leukocyte attachment and serum titers of immunoglobulin G or complement-binding anti-basement membrane zone antibodies was observed. These results suggest that immune reactants in lesional pemphigoid skin are functional complement-activating immune complexes, that differences exist between the activity of complexes in lesional and normal-appearing pemphigoid skin and may explain why lesions develop at some sites and not others.

Antigen-Antibody Complex↗
PubMed1989

Deposition of the membrane attack complex of complement in pemphigus vulgaris and pemphigus foliaceus skin.

The present study was performed to determine whether complement activation in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) results in the assembly of the terminal complement sequence or membrane attack complex (MAC) in skin lesions. Biopsy specimens of skin lesions from five patients with PV and three patients with PF contained C5, C7, C9, and the MAC related neoantigen (C5b-9 neoantigen) in intercellular substance areas (ICS), as well as IgG and the early complement components Clq, C4, and C3. The presence of these late complement components and the C5b-9 neoantigens in ICS sites of the skin lesions is indicative of complement activation by the pemphigus antibody, with subsequent assembly of the MAC. The binding of IgG and early complement components to ICS was observed in both non-lesional (normal appearing) skin and in skin lesions. However, no MAC could be detected in the normal appearing skin of our pemphigus patients. It was also noted that the MAC could be generated in vitro on cryostat sectioned normal human skin by pemphigus antibody in the presence of complement. Results of these studies suggest that complement activation may be related to membrane damage of epidermal cells in both PV and PF.

Complement Membrane Attack Complex↗
PubMed2004

Primitive complement system of invertebrates.

Most components of the human complement system have unmistakable domain architectures, making evolutionary tracing feasible. In contrast to the major genes of the adaptive immune system, which are present only in jawed vertebrates, complement component genes with unique domain structures are present not only in jawed vertebrates but also in jawless fish and non-vertebrate deuterostomes. Recent progress in genome analysis in several eukaryotes, occupying the phylogenetically critical positions, showed that most individual domains found in the complement components are metazoa specific, being found both in deuterostomes and in protostomes but not in yeast or plant. However, unique domain architecture of complement components is not present in protostomes, suggesting that the complement system has been established in the deuterostome lineage not by invention of new domains but by innovation of unique combination of the pre-existing domains. The recently assembled Ciona intestinalis draft genome contained the most modular complement genes, except for factor I. However, some possible C. intestinalis complement components show critical structural divergence from the mammalian counterparts, casting doubt on their mutual interaction. Thus, another integrative step seems to have been required to establish the modern complement system of higher vertebrates.

Animals↗
PubMed2004

Multimeric tyrosine sulfate acts as an endothelial cell protectant and prevents complement activation in xenotransplantation models.

BACKGROUND: Activation of endothelial cells (EC) in xenotransplantation is mostly induced through binding of antibodies (Ab) and activation of the complement system. Activated EC lose their heparan sulfate proteoglycan (HSPG) layer and exhibit a procoagulant and pro-inflammatory cell surface. We have recently shown that the semi-synthetic proteoglycan analog dextran sulfate (DXS, MW 5000) blocks activation of the complement cascade and acts as an EC-protectant both in vitro and in vivo. However, DXS is a strong anticoagulant and systemic use of this substance in a clinical setting might therefore be compromised. It was the aim of this study to investigate a novel, fully synthetic EC-protectant with reduced inhibition of the coagulation system. METHOD: By screening with standard complement (CH50) and coagulation assays (activated partial thromboplastin time, aPTT), a conjugate of tyrosine sulfate to a polymer-backbone (sTyr-PAA) was identified as a candidate EC-protectant. The pathway-specificity of complement inhibition by sTyr-PAA was tested in hemolytic assays. To further characterize the substance, the effects of sTyr-PAA and DXS on complement deposition on pig cells were compared by flow cytometry and cytotoxicity assays. Using fluorescein-labeled sTyr-PAA (sTyr-PAA-Fluo), the binding of sTyr-PAA to cell surfaces was also investigated. RESULTS: Of all tested compounds, sTyr-PAA was the most effective substance in inhibiting all three pathways of complement activation. Its capacity to inhibit the coagulation cascade was significantly reduced as compared with DXS. sTyr-PAA also dose-dependently inhibited deposition of human complement on pig cells and this inhibition correlated with the binding of sTyr-PAA to the cells. Moreover, we were able to demonstrate that sTyr-PAA binds preferentially and dose-dependently to damaged EC. CONCLUSIONS: We could show that sTyr-PAA acts as an EC-protectant by binding to the cells and protecting them from complement-mediated damage. It has less effect on the coagulation system than DXS and may therefore have potential for in vivo application.

Adult↗
PubMed1997

Complement receptors in HIV infection.

The complement system plays an important role in the antimicrobial defense of the organism. Its components recognize a large variety of pathogens and target them for destruction, either directly by formation of a membrane attack complex or indirectly by recruiting phagocytic cells. In addition, it has several functions in cell activation, clearance of immune complexes, control of inflammatory reactions, chemotaxis and autoimmunity. For mediation of all these tasks of the complement system, complement receptor molecules on the cell surface play a key role. Current knowledge on structure, function, signal transduction and associated molecules is briefly summarized here. The role of complement receptors for human immunodeficiency virus (HIV)-associated pathogenesis is ambiguous and varies depending on cell type. On the one hand, complement receptors support the infected host to manage HIV infection and to defend itself, at least partially, against viral spreading throughout the organism. Such complement receptor-mediated supporting mechanisms are activation of immune cells and lysis of viral particles and infected host cells. On the other hand, HIV employs complement receptors to intrude more easily into various cell types, to become localized into lymph follicles and to activate viral replication in latently infected cells. This review summarizes the complex interaction of virus and complement receptors in HIV infection for different cell types.

Animals↗
PubMed1977

Anticomplementary activity of Fusobacterium polymorphum in normal and C4-deficient sources of guinea pig complement.

Fusobacterium polymorphum has been isolated from the gingival crevice in humans and has been implicated in the immunopathology of periodontal diseases. The presence of alternative complement pathway factors in gingival crevice material suggests the contribution of this process in the manifestation of the local host response. A complement consumption assay was used to show that the anticomplementary activity of a cell-wall preparation from F. polymorphum in guinea pig complement progressed optimally at 37 degrees C and suboptimally at 0 degrees C. Similar levels of complement consumption were recorded at both temperatures, but a higher concentration of cell walls was required to demonstrate maximum activity in the cold. Augmentation experiments with additional normal and heat-treated complement showed the presence of heat-labile factors that controlled and limited the consumption of complement to a constant proportion of the total amount present. These same experiments indicated that there were no reactive antibodies in the complement used in the assay. Similar tests with C4-deficient guinea pig sera confirmed that F. polymorphum cell walls were capable of generating alternative complement pathway activity in guinea pig sera.

Cell Wall↗
PubMed1981

Activation of complement by cells infected with respiratory syncytial virus.

The ability of respiratory syncytial virus (RSV)-infected HE(p)-2 cells in culture to activate complement was investigated. After incubation of cells with various complement sources and buffer, binding of C3b to surfaces of infected cells was demonstrated by immunofluorescence with a double-staining technique. Nonsyncytial and syncytial (i.e., fused, multinucleated) cells were separately enumerated. Also, lysis of RSV-infected cells was assessed by lactic dehydrogenase release. In this system only RSV-infected cells stained for C3b, and they did so only after incubation with functionally active complement. Blocking of classical pathway activation with ethylenediaminetetraacetic acid diminished the number of infected nonsyncytial cells positively stained for C3b, but had no effect on staining of syncytial cells. Blocking of alternative pathway activation with either zymosan incubation or heat treatment decreased the number of both syncytial and nonsyncytial cells stained for C3b. Decreasing immunoglobulin concentration of the serum used as the complement source also decreased numbers of both cell types stained for C3b. Eliminating specific anti-RSV antibody diminished numbers of both cell types stained for C3b, but staining was not eliminated. Lastly, incubation with functionally active complement markedly increased lactic dehydrogenase release from infected cells. This study demonstrated that RSV-infected nonsyncytial and syncytial cells are able to activate complement by both classical and alternative pathways. Activation of complement by syncytial cells appears to be less dependent on the classical pathway than is activation by nonsyncytial cells, and activation by syncytial cells may require immunoglobulin but not specific antibody. These experiments suggest the possibility of complement activation during respiratory tract infection by RSV. Implications of this are discussed.

Antibodies, Viral↗
PubMed1989

Resistance of highly pathogenic Naegleria fowleri amoebae to complement-mediated lysis.

Weakly pathogenic and nonpathogenic Naegleria spp. are readily lysed by human and guinea pig complement. Highly pathogenic Naegleria fowleri are resistant to complement-mediated lysis. Electrophoretic analysis of normal human serum (NHS) incubated with pathogenic or nonpathogenic Naegleria spp. demonstrates that amoebae activate the complement cascade, resulting in the production of C3 and C5 complement cleavage products. To determine whether surface constituents play a role in resistance to complement lysis, trophozoites of Naegleria spp. were subjected to enzymatic treatments prior to incubation in NHS. Treatment of trophozoites with papain or trypsin for 1 h, but not with neuraminidase, increased susceptibility of highly pathogenic Naegleria fowleri to complement lysis. Treatment of trophozoites with actinomycin D or cycloheximide during incubation with NHS or pretreatment with various protease inhibitors for 4 h did not increase the susceptibility of N. fowleri amoebae to lysis. Neither a repair process involving de novo protein synthesis nor a complement-inactivating protease appears to account for the increased resistance of N. fowleri amoebae to complement-mediated lysis.

Animals↗
PubMed1996

Mesophilic Aeromonas sp. serogroup O:11 resistance to complement-mediated killing.

The complement activation by and resistance to complement-mediated killing of Aeromonas sp. strains from serogroup O:11 were investigated by using different wild-type strains (with an S-layer characteristic of this serogroup) and their isogenic mutants characterized for their surface components (S-layer and lipopolysaccharide [LPS]). All of the Aeromonas sp. serogroup O:11 wild-type strains are unable to activate complement, which suggested that the S-layer completely covered the LPS molecules. We found that the classical complement pathway is involved in serum killing of susceptible Aeromonas sp. mutant strains of serogroup O11, while the alternative complement pathway seems not to be involved, and that the complement activation seems to be independent of antibody. The smooth mutant strains devoid of the S-layer (S-layer isogenic mutants) or isogenic LPS mutant strains with a complete or rather complete LPS core (also without the S-layer) are able to activate complement but are resistant to complement-mediated killing. The reasons for this resistance are that C3b is rapidly degraded, and therefore the lytic membrane attack complex (C5b-9) is not formed. Isogenic LPS rough mutants with an incomplete LPS core are serum sensitive because they bind more C3b than the resistant strains, the C3b is not completely degraded, and therefore the lytic complex (C5b-9) is formed.

Aeromonas↗
PubMed2001

Interaction between host complement and mosquito-midgut-stage Plasmodium berghei.

After ingestion by mosquitoes, gametocytes of malaria parasites become activated and form extracellular gametes that are no longer protected by the red blood cell membrane against immune effectors of host blood. We have studied the action of complement on Plasmodium developmental stages in the mosquito blood meal using the rodent malaria parasite Plasmodium berghei and rat complement as a model. We have shown that in the mosquito midgut, rat complement components necessary to initiate the alternative pathway (factor B, factor D, and C3) as well as C5 are present for several hours following ingestion of P. berghei-infected rat blood. In culture, 30 to 50% of mosquito midgut stages of P. berghei survived complement exposure during the first 3 h of development. Subsequently, parasites became increasingly sensitive to complement lysis. To investigate the mechanisms involved in their protection, we tested for C3 deposition on parasite surfaces and whether host CD59 (a potent inhibitor of the complement membrane attack complex present on red blood cells) was taken up by gametes while emerging from the host cell. Between 0.5 and 22 h, 90% of Pbs21-positive parasites were positive for C3. While rat red and white blood cells stained positive for CD59, Pbs21-positive parasites were negative for CD59. In addition, exposure of parasites to rat complement in the presence of anti-rat CD59 antibodies did not increase lysis. These data suggest that parasite or host molecules other than CD59 are responsible for the protection of malaria parasites against complement-mediated lysis. Ongoing research aims to identify these molecules.

Animals↗
PubMed2005

Complement-mediated mechanisms in anti-GD2 monoclonal antibody therapy of murine metastatic cancer.

The role of complement in antibody therapy of cancer is in general poorly understood. We used the EL4 syngeneic mouse model of metastatic lymphoma to investigate the role of complement in immunotherapy directed against GD2, a target of clinical relevance. IgG2a and IgM anti-GD2 therapy protected EL4-challenged mice from metastases and prolonged survival. Expression of CD59, an inhibitor of direct complement-mediated cytotoxicity (CMC), effectively protected EL4 cells from CMC in vitro but did not affect the outcome of monoclonal antibody therapy. Protection by IgG therapy was also unaffected in mice deficient in C3 or complement receptor 3 (CR3) but was almost completely abrogated in FcgammaR I/III-deficient mice. These data indicate a crucial role for antibody-dependent cell-mediated cytoxicity (ADCC). However, at lower doses of IgG, therapeutic effect was partially abrogated in C3-deficient mice, indicating complement-mediated enhancement of ADCC at limiting IgG concentration. In contrast to IgG, the therapeutic effect of IgM was completely abrogated in C3-deficient mice. High level expression of CD59 on EL4 did not influence IgM therapy, suggesting IgM functions by complement-dependent cell-mediated cytotoxicity (CDCC), a mechanism thought to be inactive against tumor cells. Thus, IgG and IgM can operate via different primary mechanisms of action, and CDCC and complement-dependent enhancement of ADCC mechanisms are operative in vivo. The effects of complement can be supplemental to other antibody-mediated mechanisms and likely have increased significance at limiting antibody concentration or low antigen density.

Animals↗
PubMed2004

Complement and autoimmune glomerular diseases.

The renal glomerulus is the specialized structure in the kidney responsible for generating over 150 liters of plasma ultrafiltrate per day in humans. Certain characteristics of this structure favor involvement in autoimmune diseases. Formation of immune complexes in the glomerulus, either deposited from the circulation or generated in situ, can activate the complement system. Active products of this system include the anaphylatoxins C3a and C5a, C3b, which covalently associates with immune complexes, and the C5b-9 membrane attack complex. If complement is activated in a site accessible to blood constituents, such as in the subendothelial and mesangial regions, generated C3a, C5a and C3b can interact with their respective receptors on inflammatory cells to lead to an exudative lesion. In addition, intrinsic glomerular cells bearing relevant receptors may also be activated and can proliferate to contribute to the inflammation. In a privileged site such as the subepithelial region, complement activation products are not accessible to blood cells, and as such, the resultant pathology is noninflammatory. In this setting, effects of C5b-9 predominate, which include activation and injury of cells through still incompletely characterized pathways. Various means to alter the complement pathway are now available, including antibody inhibitors and recombinant proteins based upon naturally occurring complement regulators. The use of these agents, as well as mice in which individual components of the complement system have been deleted, has given a great deal of insight into how the complement system is involved in glomerular disease. The ability to manipulate the complement pathway is now a reality in a clinical setting, yet conclusive human studies are difficult to achieve.

Animals↗
PubMed1990

The complement system in ischemic heart disease.

The mechanisms by which tissue injury after acute myocardial infarction (AMI) occurs has not been fully elucidated. Recent evidence in experimental models has suggested involvement of the complement system in microvascular and macrovascular injury subsequent to AMI. With respect to angina pectoris, whether or not the complement system is activated is not clear. The present study assessed the role of complement as a mediator of myocardial inflammation by quantifying products of complement activation, including C3d, C4d, Bb, and SC5b-9 complexes, in 31 patients with AMI, 17 patients with unstable angina pectoris, 19 patients with stable angina pectoris, and 20 normal volunteers. The plasma C3d levels increased in patients with AMI and in those with unstable angina pectoris (p less than 0.01). The plasma levels of C4d, Bb, and SC5b-9 increased only in patients with AMI (p less than 0.01). The plasma SC5b-9 level was related to peak creatine phosphokinase (r = 0.71) and inversely related to the ejection fraction (r = -0.71). The plasma SC5b-9 level of patients with congestive heart failure was higher than that of patients without congestive heart failure in AMI. These results show that activation of complement system occurs after AMI and show an association of myocardial damage with complement activation. With respect to angina pectoris, the complement system is mildly activated in patients with unstable angina pectoris; however, the cardiac function of patients with unstable angina pectoris is not damaged. The complement system of patients with stable angina pectoris is not activated.

Angina Pectoris↗
PubMed2024

Proteomics identifies complement protein signatures in patients with alcohol-associated hepatitis.

Diagnostic challenges continue to impede development of effective therapies for successful management of alcohol-associated hepatitis (AH), creating an unmet need to identify noninvasive biomarkers for AH. In murine models, complement contributes to ethanol-induced liver injury. Therefore, we hypothesized that complement proteins could be rational diagnostic/prognostic biomarkers in AH. Here, we performed a comparative analysis of data derived from human hepatic and serum proteome to identify and characterize complement protein signatures in severe AH (sAH). The quantity of multiple complement proteins was perturbed in liver and serum proteome of patients with sAH. Multiple complement proteins differentiated patients with sAH from those with alcohol cirrhosis (AC) or alcohol use disorder (AUD) and healthy controls (HCs). Serum collectin 11 and C1q binding protein were strongly associated with sAH and exhibited good discriminatory performance among patients with sAH, AC, or AUD and HCs. Furthermore, complement component receptor 1-like protein was negatively associated with pro-inflammatory cytokines. Additionally, lower serum MBL associated serine protease 1 and coagulation factor II independently predicted 90-day mortality. In summary, meta-analysis of proteomic profiles from liver and circulation revealed complement protein signatures of sAH, highlighting a complex perturbation of complement and identifying potential diagnostic and prognostic biomarkers for patients with sAH.

Humans↗
PubMed1991

The interaction of salivary secretions with the human complement system--a model for the study of host defense systems on inflamed mucosal surfaces.

When complement first contacts salivary secretions, as when gingival crevicular fluid first meets saliva at the gingival margin, complement function is enhanced. The immediate potentiation of the complement system at equal volume ratios of serum to saliva is due to several factors, including the lower ionic strength of saliva when compared with serum and the presence of certain salivary glyproteins such as the nonimmunoglobulin agglutinins that appear to simultaneously activate C1 and affect (sequester) certain complement control proteins, such as Factor H. This initial potentiation of the complement cascade by saliva may aid in defending the area immediately above the gingival crevice from oral microbiota that are being coated with a combination of serous exudate components and salivary components. As serum becomes much more diluted with saliva (i.e., crevicular fluid moves away from the supragingival area), the acidic proline-rich salivary proteins (APRP) begin to disrupt the unbound C1q-C1r2-C1s2 macromolecular complexes. Thus, the APRP along with other C1 fixing substances in saliva appear to restrict complement function, but only when the ratios of saliva to serum exceed 250:1. Since certain salivary glycoproteins bind to viruses, the potentiation of the complement system by saliva may also play a role in neutralizing certain viral infections on mucosal surfaces where tissue transudates containing complement begin to contact mucosal secretions such as saliva. Again, the ratio of serous fluid to mucosal secretion appears to be an important factor. This article also discusses some of our preliminary data and speculations concerning the binding of the self-associating high-molecular-weight nonimmunoglobulin salivary agglutinins (NIA) with the envelope of the human immunodeficiency virus (HIV) and the possible cooperative role of C1q and fibronectin in aiding neutralization of HIV infectivity.

Complement Activation↗