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PubMed1990

Activation of complement by hemodialysis membranes: polyacrylonitrile binds more C3a than cuprophan.

Conventionally, complement activation by hemodialysis membranes has been determined by measuring fluid phase C3a. Based on such measurements, polyacrylonitrile (PAN) membranes have been classified as weak activators compared to cuprophan. Previous studies have demonstrated, however, that PAN adsorb fluid phase C3a. Based on that observation, we hypothesized that complement activation by PAN might be artifactually underestimated if relatively large amounts of C3a remained membrane bound. In the present study, a method that allows the simultaneous quantification of both fluid phase and membrane bound C3a was used to assess complement activation by PAN and cuprophan. Pieces of membrane were incubated with C3-depleted serum that had been repleted with radiolabeled C3. Subsequently, the supernates and membranes were subjected to SDS-PAGE, and complement activation was quantified by determining the radioactivity of the C3a bands in the gel. The results showed that while the serum exposed to cuprophan membranes contained almost five times more C3a than that exposed to PAN, approximately 80 times more C3a was bound to the PAN membranes. Consequently, the total amount of C3a generated in the presence of PAN was higher than that generated in the presence of cuprophan. We conclude that assessment of complement activation by hemodialysis membranes using fluid phase C3a measurements alone may be misleading.

Acrylic Resins↗

PubMed1999

Greater increase in cytokine concentration after salvage with filtered whole blood than with washed red cells, but no difference in postoperative hemoglobin recovery.

BACKGROUND: Inflammatory mediators are released in association with intraoperative and postoperative salvage of blood. Whether these mediators (cytokines) participate in the modulation of erythropoiesis or not has been investigated. STUDY DESIGN AND METHODS: Twenty-seven patients who were to undergo total knee replacement surgery were randomly assigned to postoperative blood salvage with either filtered whole blood or washed red cells. Patients with postoperative blood loss <400 mL were considered a control group. The control group did not receive any transfusions. Plasma concentrations of the anaphylatoxin C3a, the C5b-9 terminal complement complex, and the cytokines interleukins 6 and 8, hemoglobin, reticulocytes, and red cell volume fraction in the patients were repeatedly analyzed before and after surgery. RESULTS: Significantly increased concentrations of interleukin 6 appeared in all three groups, which was interpreted as a response to the surgical trauma. The increase was significantly greater in the group that received filtered whole blood after return of shed blood. The recovery of hemoglobin levels did not differ in the groups. CONCLUSION: The transfusion of filtered whole blood leads to the formation of interleukin 6 in the circulation, but postoperative hemoglobin recovery was similar in all groups.

Aged↗

PubMed2006

Complement in asthma: sensitivity to activation and generation of C3a and C5a via the different complement pathways.

Studies in rodent models suggested that complement may play a critical role in susceptibility to airway hyperresponsiveness (AHR) and as a mediator of bronchial obstruction and inflammation in asthma. Complement may participate in susceptibility to asthma because of an intrinsic abnormality in complement activation and generation of C3a, C5a, or other products that affect cellular responses, resulting in T(H)2 predominance and asthma susceptibility. Alternatively, an intrinsic abnormality in the cellular response to complement activation products could determine susceptibility to asthma. In this study, the authors investigated whether complement in patients with atopic asthma versus nonatopic controls possesses an increased propensity to become activated. Despite reports that total complement plasma levels in unchallenged asthmatics are normal, an abnormal sensitivity of complement to activation may exist if an isoform or a polymorphic variant of a complement protein was present and resulted in gain or loss of function without associated changes in total complement levels. Therefore, complement activation was induced in vitro in plasma of asthmatics and controls using activators of the classical, alternative, and lectin pathways and measured C3a, other C3 fragments, and C5a. For each pathway, similar amounts of generated fragments, as well as C3a/C3 and C5a/C5 ratios, were found in asthmatics and controls. Also, similar basal plasma levels of C3a and C5a were found in both groups; however, mannan-binding lectin (MBL) levels were moderately elevated in asthmatics. In conclusion, the results suggest that, in asthmatic patients, complement activation does not exhibit an abnormal sensitivity to activation by any of the known activation pathways.

Adult↗

PubMed1998

Molecular cloning of two isoforms of the guinea pig C3a anaphylatoxin receptor: alternative splicing in the large extracellular loop.

The anaphylatoxin C3a is released from C3 during complement activation. C3a is a potent spasmogen and has recently been described as an eosinophil and mast cell chemotactic factor that mediates a number of inflammatory reactions. Previously, we demonstrated the presence of a specific C3a receptor (C3aR) on guinea pig platelets. We report here the isolation of cDNA clones encoding for two isoforms of guinea pig C3aR (gpC3aR). Hydropathy analysis of the deduced amino acid sequence of both gpC3aR clones indicated seven transmembrane domains with a large extracellular (EC) loop between the fourth and fifth transmembrane domains, which is a known characteristic of the human C3aR. Northern blot analysis revealed that the gpC3aR was abundantly expressed on macrophages and in the spleen. A comparison of the deduced amino acid sequence of the larger gpC3aR (gpC3aR-L) with the recently cloned human C3aR indicated a 59.5% identity. The deduced amino acid sequence of the second, smaller cDNA clone was identical with gpC3aR-L, except that it lacked 35 amino acids in the large EC loop. Our evidence indicates that alternative splicing occurred in the large EC loop that accounts for these two isoforms. L cells separately expressing one of these two isoforms of the gpC3aR showed similar high-affinity C3a binding. An RT-PCR analysis documented that both forms of the C3aR were expressed in a variety of guinea pig tissues. The cloning and expression of these two natural forms of gpC3aR cDNA indicated that the deletion of the 35-residue portion of the large EC loop of gpC3aR-L did not alter C3a binding.

Alternative Splicing↗

PubMed1986

Demonstration of anaphylatoxins C3a, C4a and C5a in the scales of psoriasis and inflammatory pustular dermatoses.

Complement components C3a, C4a and C5a were assayed in corneal scale extracts from psoriasis and other dermatoses characterized by sterile subcorneal pustules, using radioimmunoassay. Larger amounts were detected in psoriasis and related pustular dermatoses than in extracts of non-inflammatory stratum corneum. It is concluded that complement is activated via the classical pathway and releases the neutrophil chemotactic fragment C5a.

Anaphylatoxins↗

PubMed1993

The adipsin-acylation stimulating protein system and regulation of intracellular triglyceride synthesis.

We have previously characterized an activity from human plasma that markedly stimulates triglyceride synthesis in cultured human skin fibroblasts and human adipocytes. Based on its in vitro activity we named the active component acylation stimulating protein (ASP). The molecular identity of the active serum component has now been determined. NH2-terminal sequence analysis, ion spray ionization mass spectroscopy, and amino acid composition analysis all indicate that the active purified protein is a fragment of the third component of plasma complement, C3a-desArg. As well, reconstitution experiments with complement factors B, D, and complement C3, the components necessary to generate C3a, have confirmed the identity of ASP as C3a. ASP appears to be the final effector molecule generated by a novel regulatory system that modulates the rate of triglyceride synthesis in adipocytes.

Amino Acid Sequence↗

PubMed2004

[Comparison of biocompatibility of hemophane, cellulose diacetate and acrilonitile membranes in hemodialysis].

INTRODUCTION: The membranes used in haemodialysis (HD) may be manufactured from cellulose, modified cellulose or synthetic polymers. Such membranes, when in contact with blood, activate the complement system, which entails changes in leukocyte (L) and platelet (P) counts. The magnitude of complement activation depends on the type of membrane used, and represents the biocompatibility index. Acrylonitrile (AN69) is synthetic membrane of high biocompatibility standards, whereas haemophane (HP) and cellulosediacetate (CD) membranes are modified cellulose-based membranes. The biocompatibly profiles of HP, CD and AN69, characterised by changes in L and P counts and activation of complement components (C3a and C5b-9), has been studied in order to assess the biocompatibility features of HP, CD and AN69 membranes. MATERIALS AND METHODS: We compared the generation of C3a des Arg and C5b-9 and the changes in L and P counts in groups of patients on HD who used HP (3 patients), CD (3 patients) and AN69 membrane (3 patients). Concentrations of C3a des Arg and C5b-9, and L and P counts were measured in the first HD session of the week, just before the start of HD (0 min) and after 15, 120 and 240 min. RESULTS: For HP, L count at 15 min had declined to 50% of the pretreatment level (p < 0.05), compared with 59.3% (p < 0.05) for CD and with 98.7% (p = ns) for AN69, returning to the pretreatment level at 240 min. Statistically significant difference was found comparing L counts for HP vs AN69 (p < 0.001) and CD vs AN69 (p < 0.001). The mean plasma concentrations of C3a des Arg were 1246 +/- 832 ng/ml for HP, 1148 +/- 774 ng/ml for CD and 639 +/- 217 ng/ml for AN69 and significant difference was found comparing HP vs AN69, CD vs AN69 (p < 0.05). The maximal values of C3a des Arg occurred at 15 min in HP and CD (p < 0.005), whilst for AN69 the concentrations showed no statistically significant differences. The plasma concentrations of C5b-9 in patients on HP and CD were the highest at 15 min (p < 0.005), while those on AN69 did not show any statistically significant rise. DISCUSSION: The fall in L counts was considerably marked for HP and CD membranes, with the lowest level at 15 min following blood exposure, thereafter returning to pretreatment level, whilst in AN69 leukopenia was not noted. The loss of L from the circulation is attributed to their pulmonary sequestration since complement activation and release of C5a fraction into the circulation results in their binding to the neutrophils and upregulation of the adhesion-promoting integrins of leukocytes, resulting in their binding to endothelial cells. The mean plasma concentrations of C3ades Arg, measured in the course of clinical use of HP and CD were significantly higher compared with synthetic membrane AN69, reaching the maximal level at 15 min. The complement activating potential of a biomaterial is one of its important biocompatibility features. The C3a complement activation curve is characteristic of cellulose-based materials and is governed by interaction between blood and hydroxyl groups on the membrane surface and by the density of hydroxyl groups available for the binding of C3b. The highest concentrations of C5b-9 in modified cellulose membranes were achieved by 15 min following blood exposure and met the activation curve for C3a. The capacity of AN69 membrane to adsorb anaphylatoxins may be a contributory factor for the failure to measure any increase in complement fraction concentration during HD for AN69. CONCLUSION: There are significant differences between HP, CD and AN69 membranes concerning complement activation magnitude and leukopenia rate. Modified cellulose membranes HP and CD induce higher C3a concentrations and superior leukopenia rate compared with AN69. Synthetic membrane AN69 proved of higher biocompatibility, with lower efficiency of complement activation.

Acrylonitrile↗

PubMed1987

Complement activation during cardiac and thoracic vascular operations.

To study complement activation, we evaluated nine patients who underwent cardiac operations requiring cardiopulmonary bypass (CPB) and nine other patients who underwent thoracic vascular operations without CPB. Concentration of C3, as measured by radioimmunoassay, was used as an indicator of complement activation (C3a is a complement-degradation product). In the CPB patients, the C3a level increased tenfold (from baseline value) after the onset of bypass, and continued to increase during bypass. Protamine produced an additional twofold increase in the C3a value, to a peak of 5461 +/- 1360 ng/ml. By 12 hours after surgery, the C3a level had decreased to normal (400 ng/ml). In the non-CPB patients, C3a remained at baseline levels until the administration of protamine, which caused a tenfold increase to a peak of 2281 +/- 293 ng/ml; C3a levels returned to normal 6 hours after operation. The peak postprotamine C3a levels were significantly higher (p < 0.01) in the CPB group than in the non-CPB group. This finding was due to the fact that, during CPB, complement activation occurs via the alternative pathway; the administration of protamine then causes additional activation via the classical pathway. During thoracic vascular operations, however, complement activation occurs only in response to protamine, via the classical pathway.

Journal Article↗

PubMed2006

The complement component C5a induces the expression of plasminogen activator inhibitor-1 in human macrophages via NF-kappaB activation.

BACKGROUND: Atherosclerosis is considered to be a chronic inflammatory disorder. Activation of the complement cascade is a major aspect of chronic inflammatory diseases. Complement components were identified in atherosclerotic plaques, and a correlation between adverse events and C5a plasma levels was found. These findings support the notion that complement activation contributes to development and progression of atherosclerotic lesions. OBJECTIVES: We investigated whether complement components C3a and C5a regulate plasminogen activator inhibitor (PAI-1) in human macrophages. METHODS: Human monocyte-derived macrophages (MDM) and human plaque macrophages were cultured and incubated with the complement component C5a. RESULTS: C5a increased PAI-1 up to 11-fold in human MDM and up to 2.7-fold in human plaque macrophages. These results were confirmed at the mRNA level using real time-polymerase chain reaction. Pertussis toxin or anti-C5aR/CD88 antibody completely abolished the effect of recombinant human C5a on PAI-1 production, suggesting a role of the C5a receptor. Experiments with antitumor necrosis factor (TNF)-alpha antibodies and tiron showed that the effect of C5a was not mediated by TNF-alpha or oxidative burst. Furthermore C5a induced NF-kappaB binding to the cis element in human macrophages and the C5a-induced increase in PAI-1 was completely abolished by an NF-kappaB inhibitor. CONCLUSIONS: We conclude that C5a upregulates PAI-1 in macrophages via NF-kappaB activation. We hypothesize that - if operative in vivo- this effect could favor thrombus development and thrombus stabilization in the lesion area. On the other hand one could speculate that C5a-induced upregulation of PAI-1 in plaque macrophages could act as a defense mechanism against plaque destabilization and rupture.

Cells, Cultured↗

PubMed1990

Determination of the epitope specificities of monoclonal antibodies using unprocessed supernatants of hybridoma cultures.

A double monoclonal antibody (mAb) ELISA has been developed to determine the epitope specificities of murine monoclonal (mAbs). It permits the mAbs which bind to the same or adjacent epitopes to be distinguished from those which bind to separate epitopes on soluble monomeric proteins. The assay is designed for the early evaluation of mAbs in hybridoma culture supernatants when purified or labeled mAbs are not available. It does not rely on chemical or enzymatic fragmentation of the antigen and does not generate results which may be due to differences in the affinities of the mAbs. Moreover the characteristic multiple binding of polyclonal antibodies to the same epitope is also avoided. A further advantage is the accessibility of epitopes on a given antigen since the antigen is presented by a solid-phase mAb, in contrast to assays in which the antigen itself is adsorbed onto the solid phase. The test was evaluated using culture supernatants from hybridomas which produced mAbs against the complement proteins C3a, C6 or C7.

Animals↗

PubMed2004

Complement activation in prestorage leucocyte-filtered plasma.

Complement activation and generation of pro-inflammatory cytokines occur during storage of blood components. Prestorage leucocyte filtration of platelet concentrates and red cells diminishes the accumulation of leucocyte-derived cytokines during storage, however, transfusion reactions are not eliminated. We investigated inflammatory mediator release during storage of plasma and whole blood and the effect of prestorage leucocyte filtration of plasma. Twenty-four blood units were collected from healthy blood donors and stored for 35 days. Eight units were stored as whole blood, eight units as plasma and eight units as prestorage filtered plasma. Samples were collected weekly for analyses of potassium, leucocytes, free plasma haemoglobin, complement activation (C3a and SC5b-9) and pro-inflammatory cytokines [interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha]. Elevated levels of C3a and SC5b-9 were registered in filtered plasma, from the beginning of storage. C3a levels increased during storage. There was a higher rate of change during storage in C3a (P < 0.01) and SC5b-9 (P < 0.05) in plasma compared with filtered plasma. Interleukin (IL)-8 is released in whole blood. The cytokine levels generated in plasma and filtered plasma were low. Complement activation is present in whole blood, plasma and filtered plasma during storage. Prestorage filtration of plasma activates the complement cascade but does not influence cytokine generation.

Blood↗

PubMed2006

Complement activation in Lyme neuroborreliosis--increased levels of C1q and C3a in cerebrospinal fluid indicate complement activation in the CNS.

A strong initial inflammatory response is important in neuroborreliosis. Since complement is a main player in early inflammation, we monitored the concentration and activation of complement in plasma and cerebrospinal fluid from 298 patients, of whom 23 were diagnosed with neuroborreliosis. Using sandwich ELISAs, we found significantly elevated levels of C1q, C4, C3, and C3a in cerebrospinal fluid, but not in plasma, in patients with neuroborreliosis. This finding indicates that complement plays a role in the human immune response in neuroborreliosis, that the immunologic process is compartmentalized to the CNS, and that complement activation may occur via the classical pathway.

Adolescent↗

PubMed2003

Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1.

Complement has recently been implicated in developmental pathways and noninflammatory processes. The expression of various complement components and receptors has been shown in a wide range of circulating myeloid and lymphoid cells, but their role in normal hematopoiesis and stem cell homing has not yet been investigated. We report that normal human CD34(+) cells and lineage-differentiated hematopoietic progenitors express the complement anaphylatoxin C3a receptor (C3aR) and respond to C3a. Moreover, C3a, but not the biologically inactive desArg-C3a, induces calcium flux in these cells. Furthermore, we found that C3 is secreted by bone marrow stroma and that, although C3a does not influence directly the proliferation/survival of hematopoietic progenitors, it (1) potentiates the stromal cell-derived factor 1 (SDF-1)-dependent chemotaxis of human CD34(+) cells and lineage-committed myeloid, erythroid, and megakaryocytic progenitors; (2) primes SDF-1-dependent trans-Matrigel migration; and (3) stimulates matrix metalloproteinase-9 secretion and very late antigen 4 (VLA-4)-mediated adhesion to vascular cell adhesion molecule 1 (VCAM-1). Furthermore, we found that murine Sca-1(+) cells primed by C3a engrafted faster in lethally irradiated animals. These results indicate that normal human hematopoietic stem and progenitor cells express functional C3aR and that the C3aR-C3a axis sensitizes the responses of these cells to SDF-1 and thus may be involved in promoting their homing into the bone marrow via cross talk with the SDF-CXC chemokine receptor-4 (CXCR4) signaling axis. C3a is the first positive regulator of this axis to be identified.

Antigens, CD↗

PubMed1987

Functional analysis and quantification of the complement C3 derived anaphylatoxin C3a with a monoclonal antibody.

The C3 fragment C3a belongs to the anaphylatoxins. It has immune regulatory activity and contributes to the pathogenesis of the adult respiratory distress syndrome (ARDS). The low molecular weight (9 kD) of C3a complicates the production of antibodies to C3a. We obtained a monoclonal antibody (designated H13) to human C3a. It reacts with C3a or C3a-desArg and with native C3 but not with C5 or C5a. In immunoblot analysis it reacts with the alpha- but not with beta-chain of C3 and binds to a protein with a mol. wt of about 10 kD present in zymosan-activated sera which is only marginally detectable in nonactivated serum and absent in plasma. H13 crossreacts with the analogous proteins of rabbit, guinea pig and sheep. H13 has the capacity to bind 125I-radiolabelled C3a efficiently but fails totally to react with 125I-C5a or with other C3 alpha-chain fragments. H13 blocks C3a functional activity. It markedly inhibits C3a-induced 3H-serotonin release from platelets in vitro and similarly inhibits the C3a-induced extravasation of Evans blue into the skin in vivo. H13 does not interfere with the haemolytic activity of C3. An ELISA system was established using H13 which permits quantification of C3a in sera of polytrauma patients. The antibody H13 should facilitate further functional analysis of C3a in experimental systems. It should be useful for quantification of C3a in diagnostic assays and also for application in immunopathology.

Animals↗

PubMed1986

Role of the N-terminal regions of hog C3a, C5a and C5a-desArg in their biological activities.

The N-terminal regions of the complement peptides C3a, C5a and C5a-desArg (purified from yeast-activated hog serum) were gradually shortened by incubation with leucine amino peptidase. This treatment led to the following changes in the biological activities of these peptides: the potencies of C5a and C5a-desArg in aggregation of human polymorphonuclear leukocytes and of guinea-pig platelets, and their ability to deactivate these cells were gradually diminished; the chemotactic effect of C5a-desArg on human leukocytes was similarly lowered, while the chemotactic potency of C5a was even increased up to the loss of the first 12 N-terminal amino acids. However, after removal of the whole N-terminal region (i.e. 20 amino acids distal of the first disulfide bridge) the potency of both peptides was decreased to a few percent. In contrast, C3a totally lost its platelet-aggregating as well as deactivating activity already after cleavage of 10-15 N-terminal amino acids by LAP. On leukocytes, on the other hand, C3a retained some activity even after the loss of the whole N-terminal region. These results indicate that the N-terminal regions play an important role for biological activities of the three complement peptides, possibly by stabilizing the optimal conformation of their C-terminal regions which contain the receptor-activating domains.

Animals↗

PubMed1995

Activation of the endothelium by IL-1 alpha and glucocorticoids results in major increase of complement C3 and factor B production and generation of C3a.

Constitutive secretion of complement C3 and factor B by the endothelial cell (EC) is lowered by therapeutic concentrations of glucocorticoids such as hydrocortisone or dexamethasone, whereas regulatory protein factor H production is increased by these hormones. In contrast, the proinflammatory cytokine IL-1 alpha has a stimulatory effect on C3 and factor B secretion by the endothelium and an inhibitory effect on factor H secretion. In this study, we examined the combined effect of IL-1 alpha and glucocorticoids on C3 and factor B expression by the endothelial cell. When dexamethasone or hydrocortisone were added to IL-1 alpha, significant potentialization of IL-1 alpha-induced stimulation of C3 and factor B production was observed, occurring at various concentrations of either stimuli. Dose-response experiments indicate that, in vitro, optimal concentrations are in the range of 10(-7) to 10(-5) M for dexamethasone and 50-200 U for IL-1 alpha. In contrast, dexamethasone counteracts, in an additive way, the inhibitory effect of IL-1 alpha on regulatory complement protein factor H production by EC. Such a potentialization between glucocorticoids and IL-1 alpha was not observed for another marker of endothelial activation, IL-1 alpha-induced stimulation of coagulation tissue factor expression. The association of glucocorticoids and IL-1 alpha therefore appears to be a specific and major stimulus for the secretion of complement C3 and factor B, two acute-phase proteins, by the endothelium. As a result of the in vitro endothelium stimulation by glucocorticoids and IL-1 alpha, C3a is generated in the vicinity of the endothelial cell. This study further suggests that complement activation, with its deleterious consequences, may result from the stimulation of endothelium in situations where high levels of IL-1 alpha and endogenous glucocorticoids coexist, such as in septic shock.

Cells, Cultured↗

PubMed1986

Interaction of prostaglandins, activated complement, and granulocytes in clinical sepsis and hypotension.

Activated complement, thromboxane A2, prostacyclin, and activated granulocytes have been implicated in hemodynamic dysfunction after trauma, in sepsis, and in hypovolemic and septic shock. This study evaluated the interaction of plasma concentrations of complement components C3a and C5a, thromboxane B2 (TxB), prostaglandin 6-keto-F1 alpha (PGI), and granulocyte aggregation in clinical sepsis and hypotension. Forty-eight critically ill patients were followed clinically for as long as 10 days. Plasma C3a, C5a, TxB, and PGI were measured daily by the radioimmunoassay method. Granulocyte aggregation, the percentage of maximum aggregation of zymosan-activated plasma standard curves, was performed with patient plasma and normal human leukocytes. Patients were studied in four groups: group I, nonseptic, normotensive; group II, hypovolemic shock, group III, normotensive severe sepsis; and group IV, septic shock. Plasma from 12 normal adults was the control value. PGI, TxB, C3a, C5a, and granulocyte aggregation in patients were greater than that in the control subjects. Granulocyte aggregation was increased in groups III and IV versus groups I and II. C3a was increased in group IV versus groups II and III. C5a and TxB did not vary between groups. PGI was greatly increased in group IV compared with groups I through III. C3a and C5a decreased in nonsurvivors. PaO2/FiO2 ratios correlated directly with PGI and inversely with C3a and TxB/PGI. Plasma PGI and C3a are increased in septic shock. C3a and TxB/PGI imbalances are involved in hypovolemic and septic shock.

Adolescent↗

PubMed1990

A factor in serum lowers resistance and opens tight junctions of MDCK cells.

During an inflammatory reaction, factors in blood affect the permeability of endothelium and possibly organ epithelium. In this study we partially characterized a factor in human and canine blood that lowered the transepithelial electrical resistance (TER) of canine kidney epithelial cells (MDCK) and examined whether vascular permeability factors [complement component C3a and C5a and platelet-activating factor (PAF)] were responsible for this reaction. C3a and C5a caused a small (10-13%) dose-related decrease in the TER (alpha = 0.05), whereas PAF had no effect. In contrast, the factor found in both serum and plasma caused a large (60-83%) dose-dependent decrease (saturated at 30%) in the TER that was reversible within 60 min. The blood factor, which does not appear to be albumin, was heat stable and has an apparent molecular mass of 67 kDa. It preferentially decreased the TER of the epithelium when it came in contact with its basolateral surface and significantly lowered the resistance within 60 min by opening the zonula occludentes. These findings suggest that C3a, C5a, and a factor in blood can directly modulate the permeability of renal epithelium.

Animals↗