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PubMed1992

Induction of C3 expression in astrocytes is regulated by cytokines and Newcastle disease virus.

Synthesis of complement proteins and their regulation in resident cells of the central nervous system are important pathophysiologic factors that can affect the outcome of inflammatory central nervous system diseases. Primary cultures of rat astrocytes constitutively express C3 mRNA and produce C3 protein; both of them were enhanced by LPS or by a live as well as inactivated Newcastle disease virus, a neurotropic paramixovirus. TNF, IL-1 beta, and IL-8 also increased the levels of C3 mRNA and protein whereas IL-1 alpha and IL-6 had no effect, although all of these cytokines are inducible by LPS. LPS stimulation in the presence of cycloheximide decreased the LPS-mediated C3 mRNA induction by 60%. These data suggest that LPS effect on C3 regulation is mediated directly by LPS as well as by LPS-induced cytokines. Interestingly, C3 mRNA induced by Newcastle disease virus or inactivated Newcastle disease virus was inhibited by protein kinase inhibitors, H-7 and staurosporine, whereas these inhibitors had no effect on C3 induction mediated by LPS or cytokines, indicating the existence of different signal transduction pathways.

Alkaloids↗

PubMed1983

Complement (C3)-receptor-mediated phagocytosis of agarose beads by mouse macrophages. I. Intracellular degradation of agarose-bound C3bi and C3b by lysosomal enzymes.

The phagocytosis by macrophages of C3bi-coated agarose beads reached a plateau after 15 min, compared with 30 min for C3b-coated beads. By using 125I-labelled C3bi or C3b coupled to the agarose beads, we found that 70% and 95% of total radioactivity were removed from the beads after 12 h and 36 h of intracellular digestion, respectively. Intracellular degradation of C3bi linked to agarose beads was also demonstrated by testing binding of monoclonal antibodies against human C3c, C3g and C3d to beads extracted from the cells after phagocytosis. Such extracted beads also showed reduced attachment to new macrophages compared with non-ingested beads. Treatment of the cells with leupeptin, an inhibitor of the lysosomal enzyme cathepsin B, or with dextran sulphate to inhibit phagosome-lysosome fusion greatly reduced the release of labelled protein from the agarose during the first 12 h. These findings show that C3bi and C3b on agarose is destroyed intracellularly by lysosomal enzymes.

Animals↗

PubMed2006

The structure of bovine complement component 3 reveals the basis for thioester function.

The third component of complement (C3) is a 190 kDa glycoprotein essential for eliciting the complement response. The protein consists of two polypeptide chains (alpha and beta) held together with a single disulfide bridge. The beta-chain is composed of six MG domains, one of which is shared with the alpha-chain. The disulfide bridge connecting the chains is positioned in the shared MG domain. The alpha-chain consists of the anaphylatoxin domain, three MG domains, a CUB domain, an alpha(6)/alpha(6)-barrel domain and the C-terminal C345c domain. An internal thioester in the alpha-chain of C3 (present in C4 but not in C5) is cleaved during complement activation. This mediates covalent attachment of the activated C3b to immune complexes and invading microorganisms, thereby opsonizing the target. We present the structure of bovine C3 determined at 3 Angstroms resolution. The structure shows that the ester is buried deeply between the thioester domain and the properdin binding domain, in agreement with the human structure. This domain interface is broken upon activation, allowing nucleophile access. The structure of bovine C3 clearly demonstrates that the main chain around the thioester undergoes a helical transition upon activation. This rearrangement is proposed to be the basis for the high level of reactivity of the thioester group. A strictly conserved glutamate residue is suggested to function catalytically in thioester proteins. Structure-based design of inhibitors of C3 activation may target a conserved pocket between the alpha-chain and the beta-chain of C3, which appears essential for conformational changes in C3.

Animals↗

PubMed1986

[Sterile eosinophilic pustulosis].

Sterile eosinophilic pustulosis (SEP) first described by Ofuji et al. in 1970 as "eosinophilic pustular folliculitis," is obviously a new entity. The majority of patients are Japanese. So far only four European cases have been reported. However, we have recently observed a 46-year-old Greek male (the fifth case in Europe) with the typical clinical features of SEP: repeated eruptions of aggregated pruritic (follicular) papulopustules (1-2 mm in diameter). The eruptions developed in slightly elevated erythematous patches localized on the extremities, face, and trunk. Histologic examination revealed intraepidermal pustules containing eosinophils and moderate dermal infiltrates with mononuclear cells and eosinophils around follicles, sebaceous glands, and vessels. In addition to the characteristic clinical and histological features, our patient showed all the typical laboratory findings previously described: negative bacterial cultures from the pustules, blood eosinophilia, increased total IgE, negative reactions to intradermal tests of recall agents. Furthermore, the rate of suppressor/cytotoxic T-cells (OKT 8-cells) in peripheral blood was significantly diminished, and mitogenic stimulation of lymphocytes in vitro was negative (decreased LTT). These laboratory data resemble the immunopathological findings in atopic diseases. On the other hand, seborrheic skin with sterile eosinophilic pustules predominantly occurring in skin areas rich in sebaceous glands seems to be another remarkable sign of SEP. The question of whether the co-incidence of atopylike immunological constellation and seborrheic skin observed in SEP has pathogenetic importance, however remains open. Apart from corticosteroids and sulfones, a favorable therapeutic effect may be obtained by inhibitors of cyclooxygenase. In our case indomethacin caused a quick and lasting therapeutical benefit.

Antibodies, Monoclonal↗

PubMed1995

Serum protects against azurophil granule dependent down-regulation of complement receptor type 1 (CR1) on human neutrophils.

We have investigated the effect of gradual degranulation on the expression of functional receptors (CR1 and CR3) on human neutrophils. Incubation with increasing concentrations of fMLP (10(-10) - 10(-7) M) translocated CR1 and CR3 to the cell surface in a similar kinetic pattern. When reaching maximal expression of receptors (10(-7) M fMLP), 78 +/- 10% and 87 +/- 9% of the total pool of CR1 and CR3, respectively, were translocated to the cell surface. To drive the mobilization process further, cytochalasin B was introduced to increase the stimulatory effect of fMLP. No further increase in CR1 surface expression was obtained. However, we found a characteristic time course of surface appearance of CR1 and CR3 with a maximal surface expression within 1 minute, followed by a time-related down-regulation of CR1 but not CR3. In addition, the total pool of CR1 in cytochalasin B treated neutrophils was reduced after 15 minutes stimulation with fMLP measured by flow cytometry and immunoblotting, indicating degradation of CR1. The down-regulation of CR1 was concomitant with a translocation of azurophil granules, in terms of upregulation of CD63. Azurophil, but not specific nor secretory, granule fractions caused a down-regulation of CR1 on fMLP activated neutrophils. The presence of human sera and serine protease inhibitor protected CR1 from down-regulation. Together, these findings indicate that intracellular stored proteases, released in the late part of the sequential mobilization process, alters the expression of functional receptors mobilized in the early part of the mobilization process. The findings also focus on the importance of the microenvironment for the net outcome of neutrophil activation in terms of functional receptor expression.

Adolescent↗

PubMed1993

Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid carriers and complement factors induced by oral contraceptives.

Three low-dose oral contraceptives Trinordiol, Gynatrol, and Marvelon, containing ethinylestradiol (EE) in combination with triphasic levonorgestrel (LNg), monophasic levonorgestrel, and monophasic desogestrel (DGS), respectively, were given to 65 healthy women, n = 21-22 in each group. Blood levels of antithrombin III (AT III), alpha 2-macroglobulin (alpha 2M) alpha 1-antitrypsin (alpha 1at), complement factors (factor B, C3, C4), pregnancy zone protein (PZP), corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG) and albumin were measured before treatment and during the first and third treatment cycles. AT III levels decreased and alpha 1at levels increased in all three groups during treatment. alpha 2M increased during cycle 3 in the Trinordiol and Gynatrol groups. CBG, PZP and SHBG levels increased in all 3 groups, the CBG and PZP increase being higher in the Marvelon group than in the Gynatrol group. Increases in SHBG levels were found in the order Marvelon > Trinordiol > Gynatrol. Plasma levels of complement factors B, C3 and C4 remained unchanged. It is concluded that the increase in alpha 1at partly compensates for the fall in AT III, that the rise in PZP presumably enhances fibrinolysis, and that LNg has higher anti-estrogenicity and androgenicity than DSG.

Adolescent↗

PubMed1991

Functional expression of furin demonstrating its intracellular localization and endoprotease activity for processing of proalbumin and complement pro-C3.

We have cloned a rat cDNA encoding furin which is structurally related to yeast Kex2 protease. Products of 88 and 94 kDa were obtained by in vitro transcription/translation of the cDNA in the absence and presence of microsomes. When the cDNA was transfected into COS-1 cells, furin was expressed as a major glycosylated form of 94 kDa, accompanied by a minor proteolytic form of 86 kDa, and found to be localized in the Golgi complex. Proalbumin and complement pro-C3 are intracellularly processed into their mature forms by cleavage at the dibasic residues Arg-Arg, a common cleavage signal found in many pro-type precursors. In cells transfected with the cDNA of C3 or albumin alone, only about half of each proform expressed was processed by an endogenous activity of the cells. When furin was coexpressed, the proforms of both C3 and albumin were completely processed into their mature forms. In addition, co-expression of rat alpha 1-protease inhibitor mutant (Met352----Arg) resulted in inhibition of the endogenous and exogenous processing activities, as observed for the naturally occurring mutant Pittsburgh which has been identified as a specific inhibitor for the processing enzyme. Taken together, these results indicate that furin is an endoprotease localized to the Golgi complex and capable of processing proalbumin and pro-C3 into the mature forms.

Amino Acid Sequence↗

PubMed1988

Regulation of acute phase protein genes by hepatocyte-stimulating factors, monokines and glucocorticoids.

The synthesis of all the major acute phase plasma proteins is stimulated in rat hepatoma and primary cultures of hepatocytes by three, structurally and functionally distinct groups of hormones: 1) hepatocyte-stimulating factors (HSF) and interleukin-6 (IL-6); 2) interleukin-1 (IL-1) and tumor necrosis factor (TNF); and 3) glucocorticoids. Each plasma protein gene requires a specific combination of these 3 hormone types for maximal expression. One set of acute phase proteins, including alpha 2-macroglobulin, alpha 1-antichymotrypsin ( = contrapsin), cysteine protease inhibitor ( = thiostatin), alpha 1-antitrypsin, ceruloplasmin and fibrinogens are predominantly regulated by the keratinocyte-derived HSF-III/-II or IL-6, while a second set of proteins, including alpha 1-acid glycoprotein (AGP), haptoglobin and complement C3 are predominantly regulated by keratinocyte-derived HSF-I, IL-1 or TNF. In conjunction with the above peptide hormones, glucocorticoids synergistically enhance the stimulated expression of most, but not all, acute phase proteins. An exceptionally strong synergy between HSF (or IL-6), IL-1 and glucocorticoids is noted for the activation of the AGP gene. To elucidate the molecular mechanisms of regulation, we have identified the cis-acting genetic elements through which all these hormones control the transcriptional activity of the AGP gene. It appears that acute phase activates a specific nuclear binding protein in the rat liver that interacts with the peptide hormone responsive element located 5 kb upstream of the transcriptional start site.

Acute-Phase Proteins↗

PubMed2006

[Complement activation and inflammation].

The complement system not only plays an important role in the defense system, but also contributes to the amplification of inflammation if activated in excess or inappropriately controlled. Complement activation through one of three pathways is tightly controlled by various regulators of complement activation (RCA) which are constitutively expressed on various cells in order to restrict excessive activation. Complement activation may generate polypeptides, so-called anaphylatoxins, and membrane attack complex (MAC) with large molecular mass. Anaphylatoxins (C3a, C4a, and C5a) produced by activation of the complement is considered to bridge innate and acquired immunity. Considering that C5a is more potent than C3a, but the serum concentration of C3 is 10 times higher than that of C5, the overall effects of C3a may be comparative with those of C5a. Since both anaphylatoxins are considered to exert their actions through rhodopsin-typed receptors, their receptor antagonists are targets for the discovery of anti-inflammatory and immune-modulating drugs. Complement activation may be related to the pathophysiology of various refractory disorders including ARDS, asthma, septic syndrome, SLE, rheumatoid arthritis, ischemia-reperfusion injury, and psoriasis etc. Pharmacological manipulation of the complement system may consist of various strategies including (1) inhibitors of complement activation at various levels, (2) receptor antagonists of anaphylatoxins, C3a and C5a, and (3) inhibitors of C5a including monoclonal antibody. Candidate agents concerning the above-mentioned manipulations have being produced and some are now in progress toward clinical trials in patients with certain diseases.

Animals↗

PubMed1999

Up-regulation of glomerular extracellular matrix and transforming growth factor-beta expression in RF/J mice.

BACKGROUND: RF/J mice were first reported as a murine model of spontaneous glomerulosclerosis by Gude and Lupton in 1960, but the precise histologic characteristics and immunopathological background of this mouse have not been investigated further. METHODS: Measurements of serum levels of immunoglobulins, anti-single strand DNA (anti-ss-DNA) antibody, complement (C3), and circulating immune complex (IC) were performed. Analyses of glomerular histological and immunopathological lesions in association with the detection of mRNA expression of collagen IV, TGF-beta, matrix protein turnover related enzymes, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2) and platelet-derived growth factor (PDGF) were also performed in young (10-week-old) and elderly (60-week-old) RF/J mice with age-matched BALB/C mice as the controls. RESULTS: High levels of serum IgA and IgG from as early as 20 weeks of age were noted in the RF/J mice. Serum anti-ss-DNA antibody of aged RF/J mice increased up to 23% of that of aged MRL-lpr/lpr mice, and serum C3 concentration significantly decreased with age, reaching lower levels than that of BALB/c mice. IgA-IC levels were significantly high compared to BALB/C mice both in the early and late stages of life, whereas IgG-IC levels were high only in mice younger than 20 weeks. Semiquantitative and quantitative analyzes of renal histopathological findings revealed significantly marked and age-related mesangial matrix expansion in RF/J mice, with increasing frequency of global glomerular sclerosis and tubulointerstitial damage. On the other hand, although precise measurements of glomerular cell numbers also showed an apparent augmentation in both young and old RF/J mice compared to BALB/C mice, glomerular cellularity decreased with age in RF/J mice. Immunohistochemical study revealed massive immunoglobulin deposition from a young age in association with significantly higher accumulation of matrix proteins, such as types I and IV collagen and laminin from the early stage of life. In addition, in these glomeruli, transforming growth factor-beta1 (TGF-beta1) was highly expressed both in young and old mice. The mRNA expression of MMP-2 was up-regulated only in the early stage of life. Although PDGF mRNA of RF/J mice was significantly up-regulated in the early stage of life, the differences between the mice disappeared in the late stage of life. CONCLUSIONS: These findings suggest that in RF/J mice, an immunopathological background inducing high serum immunoglobulin and IC levels from the early stage of life is closely related to mesangioproliferative glomerular lesions mediated by PDGF, and that development of massive extracellular matrix accumulation in glomeruli was induced by up-regulated expression of TGF-beta with inappropriate regulation of protein turnover-related enzyme production.

Age Factors↗

PubMed2006

Hyaluronan induces vascular smooth muscle cell migration through RHAMM-mediated PI3K-dependent Rac activation.

OBJECTIVE: Hyaluronan (HA) is an important constituent of the extracellular matrix and is known to regulate cellular events through binding to CD44 and the receptor for HA-mediated motility (RHAMM). Here we investigated the role of these receptors and the signaling pathways involved in HA-mediated effects in arterial smooth muscle cells (ASMC). METHODS: Effects of high-molecular weight HA (1 to 5 mg/ml) were analyzed in cultured ASMC from rat aorta. RESULTS: HA promoted actin stress fiber and lamellipodia formation and dose-dependently induced ASMC migration without effect on proliferation. Pull-down assay of Rho protein activity indicated that HA activated RhoA and Rac. HA-induced ASMC migration was not affected by the RhoA inhibitor Tat-C3 (10 microg/ml), the Rho kinase inhibitor Y-27632 (10 microM) and blocking anti-CD44 antibody ,but was reduced by the non-selective Rho protein inhibitor simvastatin (10 microM), the Rac inhibitor LT-toxin (1 mug/ml), small interfering RNA (siRNA) targeting Rac and the phosphatidyl inositol 3-kinase (PI3K) inhibitor LY294002 (25 microM), which also blocked HA-induced Rac activation. CD44 knockdown by siRNA inhibited HA-mediated RhoA activation without effect on ASMC migration. In contrast, siRNA targeting RHAMM inhibited both HA-induced migration and Rac activation. CONCLUSIONS: High-molecular weight HA independently activates RhoA and Rac through CD44 and RHAMM, respectively. HA-induced migration depends exclusively on RHAMM-mediated PI3K-dependent Rac activation.

Actins↗

PubMed1991

Identification of C3 beta chain as the human serum eosinophil cytotoxicity inhibitor.

An eosinophil cytotoxicity inhibitor (ECI) was purified from serum of a human subject with severe allergic dermatitis. Molecular weight of the isolated polypeptide (75,000) and its NH2-terminal amino acid sequence identified it as the beta chain of the C3 complement component (apparently free, but perhaps attached to very small fragments of the alpha chain). Free beta chain, prepared from normal plasma by reduction of C3, inhibited both eosinophil cytotoxicity and neutrophil adherence functions, with half-maximal activity at approximately 250 ng/ml. Apparently free C3 beta chain was detected in certain human biological fluids associated with inflammation; the presence of C3 beta chain correlated with ECI activity. This evidence demonstrates a potential role for free C3 beta chain as a suppressor of eosinophil and neutrophil functions in inflammation.

Amino Acid Sequence↗

PubMed1981

In vitro studies on cellular and humoral chemotaxis in Crohn's disease using the under agarose gel technique.

The locomotor function of polymorphonuclear cells (cellular chemotaxis) and serum chemotactic activity (humoral chemotaxis) were studied in 51 patients with Crohn's disease using a method of migration under agarose gel. To study cellular chemotaxis patient's polymorphonuclear cells were challenged against normal Zymosan activated serum and humoral chemotaxis was evaluated testing the patient's Zymosan activated serum against normal polymorphonuclear cells. Cellular chemotaxis in the Crohn's disease group was normal (although 30% of the 51 patients had migration values out of the normal range), while humoral chemotaxis was significantly lower in Crohn's disease patients than in the control group. However, the value of humoral chemotaxis in the group of Crohn's disease patients treated with steroids was lower than that of patients not treated, thus accounting for the low mean value observed inthe Crohn's disease-group as a whole. The present results suggest that a defective chemotactic response may occur in some Crohn's disease patients, particularly during steroid treatment. These findings might be related either to a defective generation of complement derived chemotactic factors or to the presence of circulating inhibitors.

Adrenal Cortex Hormones↗

PubMed1986

Hypocomplementemia with low C1s-C1 inhibitor complex in systemic lupus erythematosus.

Ninety-three serum and plasma samples from 45 patients with systemic lupus erythematosus were analyzed for the complex formed by C1s and its inhibitor, as well as for C3, C4, C4a desarginine, and staphylococcal protein A-bound immune complexes. There were statistically significant correlations between C1s-C1 inhibitor complex and CH50, between C1s-C1 inhibitor complex and C4, and between C1s-C1 inhibitor complex and C4a desarginine. Serial studies were performed on 24 patients over a period of 6 months. Seven of 21 patients with hypocomplementemia had persistently normal levels of C1s-C1 inhibitor complex, 7 had transiently abnormal levels of C1s-C1 inhibitor complex, and 7 had sustained abnormal levels of C1s-C1 inhibitor complex. Two of 3 pregnant patients with normal levels of complement had abnormal levels of C1s-C1 inhibitor complex. Staphylococcal protein A-bound immune complexes demonstrated no correlation with any of the complement assays. Complement activation, as measured by C1s-C1 inhibitor complex, is often a transient phenomenon in systemic lupus erythematosus patients with persistent hypocomplementemia.

Antigen-Antibody Complex↗

PubMed1991

Arthritis induced immunologically with cationic amidated bovine serum albumin in the guinea pig. A morphological and biochemical study on the destruction of articular cartilage.

Arthritis was induced by injecting cationic amidated bovine serum albumin (aBSA) (pI approximately 9.2) into the knee joint of immunized guinea pigs and the mechanisms of articular cartilage destruction were studied morphologically and biochemically. Marked synovitis associated with polymorphonuclear leukocyte (PML) infiltration occurred within 1 day of the challenge. Articular cartilage infiltrated by PMLs was almost completely destroyed after 2 weeks. During the initial destructive process, proteoglycans were depleted from the cartilage and later collagen fibers disappeared. Granulation tissue growing in the inflamed synovium and bone marrow replaced the destroyed cartilage and joint cavity and formed fibrous scar tissue (fibrous ankylosis) by 8 weeks. Subsequently, the knee joints developed cartilagenous ankylosis by 12 weeks and finally bony ankylosis at 28 weeks. Autoradiography using 125I-aBSA and immunofluorescence studies for immunoglobulin (IgG) and complement (C3) demonstrated that the antigen is trapped in all zones of the articular cartilage and serves as a trigger for immune complex formation. Significantly increased neutral proteinase activities against substrates of proteoglycan subunits, [3H]carboxymethylated transferrin and L-pyroglutamyl-L-prolyl-L-valine-paranitroanilide were detected in homogenates of the synovium and cartilage from arthritic knee joints 1 and 2 weeks after induction. Inhibitor studies and pH curves suggested that the proteinase is leukocyte elastase. Measurable amounts of gelatinolytic activity, detected by activation with 4-aminophenylmercuric acetate and inhibited with EDTA, were also present in the same samples, but there was no detectable collagenase activity. The data on SDS-gelatin substrate gel showed that the proteinase is gelatinase derived from PMLs. These results suggest that in aBSA-induced arthritis, elastase and gelatinase from PMLs invading articular cartilage may play important roles in cartilage destruction.

Amino Acid Sequence↗

PubMed1986

Agglutination of sheep erythrocyte-rabbit antibody complexes treated with sheep serum by a rabbit antiserum specific for the third component (C3) of sheep complement.

Sheep E-rabbit A incubated with sheep serum for up to 20 min at 39 degrees C and washed were agglutinated by a rabbit antiserum (anti-inulin-foetal lamb serum) that was specific for sheep C3. If incubated for longer than 20 min at 39 degrees C, there was less sensitisation. Such a complex was not readily generated at 17 degrees C whereas there was no reaction if incubated at 2 degrees C. Once the sheep E-rabbit A-sheep C complex had been generated at 39 degrees C and washed free of sheep serum, it could still be agglutinated after overnight storage at 4 degrees C. Addition of chelators of Ca2+ and/or Mg2+ or antrypol or cobra venom factor (a specific inhibitor of C3) prevented sensitisation of sheep E-rabbit A by sheep serum for agglutination. These results show that sheep serum C3 was taken up by sheep E-rabbit A and its presence on this indicator demonstrated by agglutination using a rabbit antiserum specific for sheep C3.

Animals↗

PubMed2002

How antibodies to a ubiquitous cytoplasmic enzyme may provoke joint-specific autoimmune disease.

Arthritis in the K/BxN mouse model results from pathogenic immunoglobulins (Igs) that recognize the ubiquitous cytoplasmic enzyme glucose-6-phosphate isomerase (GPI). But how is a joint-specific disease of autoimmune and inflammatory nature induced by systemic self-reactivity? No unusual amounts or sequence, splice or modification variants of GPI expression were found in joints. Instead, immunohistological examination revealed the accumulation of extracellular GPI on the lining of the normal articular cavity, most visibly along the cartilage surface. In arthritic mice, these GPI deposits were amplified and localized with IgG and C3 complement. Similar deposits were found in human arthritic joints. We propose that GPI-anti-GPI complexes on articular surfaces initiate an inflammatory cascade via the alternative complement pathway, which is unbridled because the cartilage surface lacks the usual cellular inhibitors. This may constitute a generic scenario of arthritogenesis, in which extra-articular proteins coat the cartilage or joint extracellular matrix.

Animals↗

PubMed2000

Proteolytic activities of two types of mannose-binding lectin-associated serine protease.

Mannose (or mannan)-binding lectin (MBL) is an oligomeric serum lectin that plays a role in innate immunity by activating the complement system. In human, two types of MBL-associated serine protease (MASP-1 and MASP-2) and a truncated protein of MASP-2 (small MBL-associated protein; sMAP or MAp19) are complexed with MBL. To clarify the proteolytic activities of MASP-1 and MASP-2 against C4, C2, and C3, we isolated these two types of MASP in activated forms from human serum by sequential affinity chromatography. On an anti-MASP-1 column, MASP-2 passed through the column in the presence of EDTA and high salt concentration, whereas MASP-1 was retained. Isolated MASP-1 and MASP-2 exhibited proteolytic activities against C3 and C4, respectively. C2 was activated by both MASPs. C1 inhibitor (C1 INH), an inhibitor for C1r and C1s, formed equimolar complexes with MASP-1 and MASP-2 and inhibited their proteolytic activities.

Binding, Competitive↗