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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have suggested that plasma fibronectin is a component of the physiological antithrombotic mechanism and is related to resistance to cardiopulmonary failure during sepsis. The current study addresses the hypothesis that fibronectin deficiency results in increased sensitivity to thrombosis during sepsis, whereas increased fibronectin results in enhanced resistance. Rats were injected with purified fibronectin, antiserum to fibronectin, antiserum to albumin or vehicle prior to intraaortic infusion of saline, live Escherichia coli (10(7)--10(8)/100 gm) or E coli endotoxin (0.001--0.1 mg/100 gm). Infusion of the higher doses was associated with greater mortality in antifibronectin groups than the other groups. Mean arterial blood pressure fell transiently in all groups following injection of antifibronectin but not following the other pretreatment. Both endotoxin and bacterial infusion resulted in severe thrombocytopenia in antifibronectin-treated animals and to a lesser extent following antialbumin. Fibrinogen consumption was increased in all groups after antifibronectin treatment in bacteria infused animals after pretreatment with antialbumin or fibronectin. Fibrin degradation products were increased by bacterial infusion in animals treated with either antiserum. The current data support a relationship between plasma fibronectin and resistance to thrombosis. The relationship was not as clear-cut as that previously observed for nonseptic thrombotic states.
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PMID:Plasma fibronectin and resistance to thrombosis during sepsis. 675 30

Progressive multiple organ failure in association with septic complications in the surgical, trauma and burn patient is of major clinical importance. Reticuloendothelial system host defense mechanisms are abnormal following severe trauma and burn. Failure in systemic host defense is, in part, mediated by a deficiency in a circulating opsonic alpha 2 surface binding (SB) glycoprotein. This opsonic deficiency and reticuloendothelial host defense failure appears etiologic in the genesis of organ failure with sepsis. Opsonic alpha 2SB glycoprotein is identical to cold-insoluble globulin or plasma fibronectin. Plasma fibronectin is antigenically related to cell surface fibronectin which appears to be synthesized by both fibroblasts and vascular endothelial cells. Although these two proteins are antigenically related, they may or may not be identical with respect to biochemical properties and function. Cell surface fibronectin appears to be an adhesive glycoprotein mediating cell-cell interaction and cell adhesion to a substratum. Plasma fibronectin is a more soluble form which mediates reticuloendothelial or macrophage clearance of particulates such as fibrin microaggregates, collagenous debris, perhaps other bacterial or nonbacterial particulates. Since opsonic glycoprotein is identical to cold-insoluble globulin which can be readily concentrated in plasma cryoprecipitate, it has been shown that cryoprecipitate infusion can reverse opsonic deficiency in the injured patient with sepsis. Reversal of opsonic deficiency by cryoprecipitate infusion results in a marked improvement in cardiopulmonary function which includes a decline in the pulmonary shunt, a decrease in the physiologic dead space, an increase in limb blood flow, an increase in reactive hyperemia of the peripheral circulation and an increase in limb oxygen consumption. This cardiopulmonary response is paralleled by a decline in the septic state and normalization of other hematologic parameters. These studies suggest an important homeostatic role for fibronectins in organ and microvascular integrity, especially in the septic injured patient. Cell surface fibronectin which participates in cell adhesion may, in part, modulate microvascular integrity, vascular permeability and would repair. In contrast, the more soluble plasma fibronectin or opsonic alpha 2SB glycoprotein may mediate reticuloendothelial clearance of blood-borne particulates to prevent pulmonary and peripheral vascular microembolization and organ injury. Thus, reversal of opsonic deficiency may be an effective modality of therapy in the septic injured patient with organ failure.
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PMID:Plasma fibronectin (opsonic glycoprotein): its synthesis by vascular endothelial cells and role in cardiopulmonary integrity after trauma as related to reticuloendothelial function. 676 91

The reticuloendothelial system (RES) is thought to ensure organ integrity following trauma, burn, and sepsis by removing potentially embolic particulate matter and blood-borne bacteria from the circulation. Blockade of the RES with foreign colloids is known to result in a consumptive depletion of opsonic fibronectin, which modulates reticuloendothelial function, and an increase in lung localization of test particles. We investigated the role of neutrophils as a contributing factor in the increased localization of blood-borne bacteria in the lung after blockade. RE blockade induced by gelatin-coated colloid particle injection resulted in an acute (15-minute) increase in the number of 51Cr-labeled neutrophils localized in the lung, with return to control levels at 60 minutes after blockade. Fibronectin administration following blockade resulted in a significant (P less than 0.05) prolonged retention of neutrophils in the lung up to 2 hours after blockade. A parallel increase (P less than 0.05) in lung localization of heat-killed 14C-labeled Pseudomonas aeruginosa following colloid-induced RE blockade was observed, and fibronectin further increased the number of bacteria localized in the lung. Experimentally induced neutropenia abrogated the effect of colloid injection on lung localization of bacteria. It is concluded that a particulate load results in simultaneous RE blockade and neutrophil margination in the lung, both of which contribute to the increase in lung localization of bacteria. A mechanism for neutrophil-mediated pulmonary injury related to RE dysfunction following trauma is proposed.
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PMID:Neutrophil-mediated lung localization of bacteria: a mechanism for pulmonary injury. 679 Dec 89

Plasma fibronectin is a nonspecific opsonin which mediates phagocytosis of particulate matter by macrophages. Fibronectin depletion results in depression of reticuloendothelial system phagocytic function. This may potentiate microvascular embolization and sludging in critical illness. It has been hypothesized that sepsis is a major cause of fibronectin depletion. To explore this hypothesis, plasma fibronectin concentrations were measured in rats with intraabdominal abscesses and in rabbits subjected to the generalized Shwartzman reaction (spaced doses of endotoxin). In both groups of animals there was a significant increase (P less than 0.05) rather than decrease in fibronectin concentrations at times when sepsis and disseminated intravascular coagulation were manifest. This study does not support the hypothesized relationship between sepsis and fibronectin depletion. Until the kinetics of fibronectin production and utilization are further delineated, caution must be exercised in the interpretation of immunoreactive plasma fibronectin levels.
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PMID:Plasma fibronectin concentration in animal models of sepsis and endotoxemia. 682 8

Opsonic fibronectin modulates reticuloendothelial (RE) uptake of nonbacterial particulates, as well as some bacterial strains, and may thus play an important role in host defense against sepsis after burn injury. We evaluated the relationship between burn injury, sepsis, and opsonic fibronectin levels in rats, as well as the ability to reverse the acute opsonic deficiency after burn injury by administration of purified opsonic fibronectin. Burn injury resulted in an acute (within one hour) depletion of opsonic fibronectin (from 341 +/- 30 to 98 +/- 7 mg/L) that was correctable by administration of purified opsonic fibronectin when accompanied by moderate sepsis, while burn injury plus severe sepsis (level, 168 +/- 30 mg/L) limited attempted restoration of normal opsonic levels (level, 121 +/- 18 mg/L). The in vitro serum opsonic deficit was partially correctable (from 2.2% to 6.7% of the injected dose per 100 mg), while in vivo RE functional deficits could not be corrected. We conclude that the acute postburn deficiency in opsonic fibronectin is amenable to repletion therapy; however, many additional factors may contribute to acute RE failure after burn injury.
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PMID:Correction of serum opsonic defects after burn and sepsis by opsonic fibronectin administration. 682 34

An acute depletion of plasma fibronectin or FN has been observed in critically ill, surgical, or trauma patients, but there is little information on the relationships between FN levels and the final outcome in such cases, and on the simultaneous behaviour of other serum proteins. The daily values of FN, antithrombin III, IgG, C3, prealbumin, and transferrin were monitored in 98 intensive care patients after major elective surgery or trauma. According to their clinical course, they were divided retrospectively into three groups. Group A (33 patients) had sepsis. Group B (31 patients) had nonseptic complications, and group C (34 patients) had no complications in the ICU. The individual, nadir levels of FN, AT III, prealbumin, and transferrin were lower (p less than 0.01) in the septic group A than in B and C. Within the septic group, the nadir levels of AT III, but not those of FN, were lower (p less than 0.01) in the 14 nonsurvivors than in the 19 survivors. The FN and AT III levels had returned at least temporarily to the normal range in the six ultimate fatalities from sepsis who survived for more than two weeks. In the septic group, transferrin showed the highest percentages of actually subnormal levels and differed from FN in this respect with p less than 0.05. Furthermore, all six proteins showed a significant overall pattern (p less than 0.01) of parallel variations. The results confirm other reports on the behavior of fibronectin in septic patients as a group, but it was not informative as to the individual outcome, and its reduction might be viewed as part of a general plasma protein depletion associated with acute septic disease. This pattern is probably attributable to a combination of intravascular consumption and an overall excess of protein catabolism over synthesis.
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PMID:Plasma fibronectin and associated variables in surgical intensive care patients. 683 Mar 38

The opsonic activity of plasma fibronectin is important in modulating the reticuloendothelial system (RES) phagocytic removal of a variety of endogenous and exogenous particulate material from the vascular compartment. Purification of plasma-opsonic fibronectin by affinity chromatography with gelatin-Sepharose revealed that although in vitro hepatic Kupffer cell phagocytosis was absolutely dependent upon the presence of fibronectin, the purified fibronectin evaluated in concentrations similar to that found in plasma (350-450 micrograms/ml) supported phagocytosis at a level two- to threefold less than that observed in whole plasma. In contrast, the combination of purified fibronectin with small aliquots of opsonically inactive fibronectin-free plasma restored normal opsonic activity as assessed by liver slice bioassay and enhanced fibronectin-mediated attachment of gelatinized particulate to isolated Kupffer cells in vitro. Evidence is presented in this study that there exists in plasma a macromolecular species that amplifies the opsonic activity of fibronectin in a dose-related manner. This amplification or cofactor activity is nondialysable and has a molecular weight greater than 12,000. Inactivation of the amplification activity present in affinity-absorbed plasma can be achieved by heating the fibronectin-free plasma at 60 degrees C for 20 min, supporting the hypothesis that the cofactor is a protein. The amplification response is dose related, suggesting that the mechanism of its action is stoichiometric rather than catalytic. Evidence is presented that partial purification of the cofactor can be achieved by (NH4)2SO4 precipitation at 4 degrees C. Purification of this cofactor will provide an opportunity to evaluate its role in the altered opsonic states known to exist after trauma, burn, and sepsis.
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PMID:Amplification of the opsonic activity of fibronectin by a plasma factor lacking gelatin affinity. 683 58

Opsonic fibronectin is known to modulate macrophage (RE cell) and neutrophil Phagocytic function. Its depletion has been documented following trauma, burn, and operation in patients with rapid restoration of normal levels unless bacteremia and/or wound sepsis intervenes. Sepsis is associated with a secondary phase of opsonic fibronectin deficiency. We have observed in burn patients that this secondary phase of opsonic fibronectin depletion following trauma and burn is seen two to three days prior to the onset of clinical sepsis, raising the question of whether this deficiency sensitized the host to the subsequent development of sepsis or whether its deplection was merely an unsuspected sensitive indication of preclinical sepsis. To address the possibility that opsonic fibronectin deficiency might lower resistance to sepsis, Sprague-Dawley rats (200 gm) were partially depleted (35%) of their opsonic fibronectin prior to intraperitoneal inoculation with Staphylococcus aureus. Mortality to S. aureus peritonitis was significantly (p < 0.05) increased in animals with fibronectin deficiency. Furthermore, in control animals, nonsurvival was also associated with significantly (p < 0.05) lower initial fibronectin levels than survival. However, peritonitis itself also resulted in an early (within one hour) depletion of opsonic fibronectin followed by a marked "hyperopsonemia" within 12 hours in both groups. Thus, opsonic fibronectin depletion decreases resistance to sepsis, and the development of sepsis itself will initiate opsonic fibronectin deficiency. Host defense against infection may depend on early restoration and maintenance of normal opsonic fibronectin levels following trauma, burn, and operation, as well as the ability of the host to mount an appropriate hyperopsonemic elevation of fibronectin levels in response to infection.
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PMID:Opsonic fibronectin deficiency and sepsis. Cause or effect? 705 44

Reticuloendothelial (RE) clearance dysfunction, which can be induced by opsonic fibronectin deficiency, has been correlated with organ failure during sepsis. We investigate the role of opsonic fibronectin deficiency and RE blockade in modulating alterations in intestinal transvascular fluid balance induced by Pseudomonas bacteremia using an isolated, innervated, and autoperfused canine small intestinal segment. Intravenous infusion of gelatin-coated particles was used to induce fibronectin deficiency and RE blockade. Lymph flow and lymph/plasma (L/P) protein concentration ratios were stable following intravenous challenge with bacteria or gelatin-coated particles. In contrast, lymph flow increased and L/P ratio decreased significantly when bacteremia coexisted with particle-induced opsonic fibronectin deficiency and RE blockade. This elevation in lymph flow and decline in L/P ratio was associated with normal vascular permeability to albumin, IgG, and IgM. The increase in intestinal fluid flux during bacteremia with RE blockade appears to be due to an increase in microvascular hydrostatic pressure and not to an increase in vascular permeability. These findings emphasize a potentially important role for fibronectin and associated RE system function as determinants of fluid filtration during sepsis.
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PMID:Fibronectin deficiency and intestinal transvascular fluid balance during bacteremia. 706 70

Opsonic fibronectin is known to mediate reticuloendothelial (RE) cell and neutrophil uptake of nonbacterial particulates. In a recent study opsonic fibronectin deficiency following burn preceded the onset of sepsis, leading us to hypothesize a role for this protein in antibacterial defense. To test this hypothesis we compared pooled normal human serum to fibronectin-depleted serum in its ability to opsonize and promote phagocytosis of Staphylococcus aureus by human neutrophil monolayers. Phagocytosis and intracellular killing were evaluated using acridine orange staining and ultraviolet (UV) microscopy. Human serum depleted of opsonic fibronectin by gelatin-sepharose affinity chromatography manifested a marked reduction in its ability to support phagocytosis of S aureus by human neutrophils. Reconstitution of fibronectin-deficient human serum with purified human plasma fibronectin restored its opsonic activity. The direct interaction of fibronectin with the bacteria was shown by mixing and/or incubation of the bacteria with normal serum followed by centrifugation and removal of the bacteria. This resulted in a marked (P less than 0.05) depletion (adsorption) of the fibronectin from the serum. Fibronectin appears not to act independently, but was an important cofactor in the ability for serum to stimulate phagocytosis. Thus, plasma fibronectin may be an important protein essential for maximal opsonic activity of serum. Its depletion following trauma and burn may undermine RE cell and neutrophil defense against infection and bacteremia, thus contributing to organ failure during septic shock.
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PMID:Opsonic fibronectin is necessary for optimal serum-mediated phagocytosis of Staphylococcus aureus by human neutrophils. 713 37


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