Plasma fibronectin (opsonic glycoprotein): its synthesis by vascular endothelial cells and role in cardiopulmonary integrity after trauma as related to reticuloendothelial function.
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.
D000818:Animals; D002199:Capillary Permeability; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D006321:Heart / Q000503:physiopathology; D006487:Hemostasis; D006801:Humans; D005779:Immunodiffusion; D007728:Kupffer Cells / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000503:physiopathology; D012157:Mononuclear Phagocyte System / Q000276:immunology* / Q000503:physiopathology; D010587:Phagocytosis; D012772:Shock, Septic / Q000276:immunology* / Q000503:physiopathology
D005353:Fibronectins