Mitochondria, the powerhouses of our cells, are remnants of a eubacterial endosymbiont. Notwithstanding the evolutionary time that has passed since the initial endosymbiotic event, mitochondria have retained many hallmarks of their eubacterial origin. Recent studies have indicated that during perturbations of normal homeostasis, such as following acute trauma leading to massive necrosis and release of mitochondria, the immune system might mistake symbiont for enemy and initiate an inappropriate immune response. The innate immune system is the first line of defense against invading microbial pathogens, and as such is the primary suspect in the recognition of mitochondria-derived danger-associated molecular patterns and initiation of an aberrant response. Conversely, innate immune mechanisms are also central to noninflammatory clearance of innocuous agents. Here we investigated the role of a central humoral component of innate immunity, the lectin pathway of complement, in recognition of mitochondria in vitro and in vivo. We found that the soluble pattern recognition molecules, mannan-binding lectin (MBL), L-ficolin, and M-ficolin, were able to recognize mitochondria. Furthermore, MBL in complex with MBL-associated serine protease 2 (MASP-2) was able to activate the lectin pathway and deposit C4 onto mitochondria, suggesting that these molecules are involved either in homeostatic clearance of mitochondria or in induction of untoward inflammatory reactions. We found that following mitochondrial challenge, C3 was consumed in vivo in the absence of overt inflammation, indicating a potential role of complement in noninflammatory clearance of mitochondria. Thus, we report here the first indication of involvement of the lectin pathway in mitochondrial immune handling.
Abstract We describe a double-antibody enzyme immunoassay for determination of free thyroxin (FT4) in dried blood samples on filter paper, with use of a T4-beta-D-galactosidase complex. The measurable range of FT4 concentration in two 3-mm blood discs, each of which contained about 2.7 microL of blood, was 1.9 to 93 ng/L, as determined by comparison with concentrations of FT4 in known serum standards. FT4 in blood samples dried on filter paper was stable for at least four weeks when kept dry at -20 degrees C, room temperature, or 37 degrees C. The mean coefficients of variation were 7.6% (within assay) and 6.4% (between assays). Results for FT4 by this method correlated well with those for serum determined by radioimmunoassay (r = 0.98). The proposed method can be used to differentiate persons with hyper- and hypothyroidism from normal subjects and those with abnormal concentrations of thyroxin-binding globulin. The procedure seems suited for screening studies.
AbstractBackground: A stapler is usually used for transection and closure of the pancreas in distal pancreatectomy (DP) or central pancreatectomy (CP). When the pancreas is transected to the right of the portal vein, it is difficult to use a stapler and clinically relevant postoperative pancreatic fistula (CR-POPF) frequently occurs. We report on the efficacy of pancreaticojejunostomy (PJ) of the pancreatic stump for patients in whom stapler use is difficult. Methods: Patients who underwent DP or CP were enrolled in this study. The pancreas was usually transected by a stapler, and ultrasonic coagulating shears (UCS) were used depending on the tumor situation. When using UCS, hand-sewn closure or PJ was performed for the pancreatic stump. The relationship between clinicopathological factors and the methods of pancreatic transection and closure were investigated. Results: In total, 164 patients underwent DP or CP, and the pancreas was transected with a stapler in 150 patients and UCS in 14 patients. The rate of CR-POPF was higher and the postoperative hospital stay longer in the stapler group than in the UCS group.PJ of the pancreatic stump, which was performed for 7 patients, did not worsen intraoperative factors. CR-POPF was not seen in these 7 patients, which was significantly less than that with hand-sewn closure. Conclusions: PJ of the pancreatic stump during DP or CP reduces CR-POPF compared with hand-sewn closure and may be useful especially when the pancreas is transected to the right of the portal vein.
Ficolin is a multimeric protein consisting of an N-terminal collagen-like domain and a C-terminal fibrinogen-like domain. The structure is similar to mannose-binding lectin (MBL) and complement C1q owing to the collagen-like stalk. Accumulating data indicate that a key function of ficolin is to recognize the carbohydrate moieties on pathogens as a pattern-recognition molecule. Two or three kinds of ficolin have been identified in each species of mammals. They are similar but with some differences in the expression site, location site, ligand-binding specificity and ability to form complexes with MBL-associated serine proteases (MASPs). Like MBL, some ficolins are serum lectins and can form a complex with MASPs and small MBL-associated protein (sMAP). This complex activates the complement through "the lectin pathway". Our recent study suggests that ficolin acts through two distinct routes: the lectin pathway and a primitive opsonophagocytosis. All these observations suggest that ficolins function in clearance of non-self, based on their location sites and their molecular features.
