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纖維介質加強宿主之防衛作用
Effect of Fibronectin on Host Defense
摘要
纖維介質（fibronectin）是一種大分子的醣蛋白，廣泛分佈於人類體液和間質組織中。體液中的纖維介質一般以雙元體存在，而細胞或組織上的纖維介質則以多元體存在。纖維介質含有多個不同結合部位，可以和不同分子或細胞相作用。這些不同的互相作用各有其特殊功能：包括加強細胞吸附（attachment）、被展（spreading）和分化（differentiation）；並促進血液凝固（coagulation）、傷口癒合、和網狀內皮系統功能（reticuloendothelial clearance）等。以常見致病菌作為標的物進行研究，結果發現纖維介質對金黃色葡萄球菌和表皮葡萄球菌具有調理作用，纖維介質對大腸桿菌或B族鏈球菌沒有直接的調理作用，但可作用在吞噬細胞加強其自抗體所仲介的調理吞噬作用。研究也顯示纖維介質既促進吞噬作用也增加細胞內的呼吸代謝反應；但却不會增加細胞外超氧根離子釋放去傷害組織。進一步研究纖維介質促進吞噬細胞功能的機轉發現，纖維介質是透過GTP結合蛋白（G-protein）來影響吞噬細胞的骨架整合，和細胞內鈣離子之游動；進而促進吞噬細胞功能。因此對於纖維介質較低的新生兒、嚴重外傷或燒傷病人，為防患或治療其細菌性感染，應考慮投與纖維介質以增強其宿主防衛功能。
並列摘要
Fibronectin (Fn) is a high molecular weight glycoprotein which possesses a number of cell binding sites that allow attachment of the molecule to certain bacteria and a variety of human cells intracellular matrix where it promotes cell to cell adhesion and maintains vascular integrity. Circulating or plasma Fn has been shown to enhance reticuloendothelial clearance of particles. The effects of Fn on host defense against microorganisms are not completely under stood. Employing common bacterial pathogens as targets, we found that Fn appeared to act as a bridge between PMNs and staphylococci to promote opsonic activity. Fibronectin did not directly interact with GBS but acted on phagocytes to augment IgG-mediated phagocytosis of GBS. As demonstrated with a fluorescence activated cell sorter (FACS), Fn significantIy enhanced IgG Fc receptors expression on the surface of PMNs. Studies of CL and superoxide production showed that. Fn significantIy enhanced the CL response of PMNs to staphylococci and antibody-opsonized GBS. The intracellular metabolic inhibitor NaN3 but not the extracellular scavengers superoxide dismutase or human serum albumin inhibited Fn-enhanced CL. Thus, Fn did not appear to promote extracellular release of superoxide by PMNs stimulated by these unopsonized or antibody-opsonized bacteria. These data suggest that Fn enhances phagocytosis and intracellular digestion of bacteria without promoting release of toxic oxygen radicals into the surrounding tissues. The mechanisms by which Fn enhanced phagocytosis and respiratory burst were mediated through a pertussis toxin-sensitive GTP binding protein which likely promotes actin polymerization and intracellular calcium mobilization via different pathways. In concIusion, Fn significantly promotes phagocyte functions via a PT-sensitive G protein. Optimal immunotherapy for treatment and prevention of bacterial sepsis in neonates and patients with trauma or bum, who have low Fn and antibody levels, may involve the administration of both Fn and antibody.