Acetaminophen liver injury: sequential changes in two biochemical indices of regeneration and their relationship to histologic alterations

Massive liver injury was produced in fasting male Sprague-Dawley rats weighing 200 +/- 25 gm each by gastric administration of 1400 mg/kg acetaminophen. The time sequence of changes in liver ornithine decarboxylase (ODC) activity, which reflects the earliest phases of cell multiplication, liver thymidine kinase (TK) activity, which reflects DNA synthesis, and liver histology (necrosis, mitosis, and repair processes) was recorded. ODC showed the usual biphasic response. By 12 hours, it reached its first peak, a six- to eightfold increase. At this time there was no histologic evidence of necrosis, and serum malate dehydrogenase (MDH), sorbitol dehydrogenase (SDH), and alanine aminotransferase (SGPT) were normal. During the next 12 hours ODC decreased by 60% to 70% and cellular necrosis became evident, and reached a peak at 24 to 36 hours, as did serum MDH, SDH, and SGPT. The serum enzymes fell precipitously at 48 hours, but the histologic evidence of necrosis subsided gradually over 60 hours. The secondary ODC peak, a fourfold increase, coincided with rising activity of TK, which increased 25- to 35-fold over 54 to 72 hours, and then subsided. At 54 hours, when DNA synthesis had already peaked, there was no histologic evidence of repair other than mitoses. However, within the next 6 hours, evidences of repair became prominent, and remained so for another 36 hours before subsiding. Thus, with acetaminophen injury, the initial phases in preparation for cell multiplication occurred before histologic evidence of injury was apparent, and DNA synthesis peaked before other evidence of tissue repair became evident.(ABSTRACT TRUNCATED AT 250 WORDS)     

派罗欣治疗慢性乙肝18例临床观察

目的：探讨派罗欣治疗慢性乙肝的临床疗效。方法：18例慢性乙肝患者采用派罗欣治疗。肝脏组织损伤程度采用Knodell计分法、血清HBVDNA采用PCR技术及肝功能检测，并对治疗前后的检测结果进行比较。结果：与治疗前相比，治疗后肝组织坏死及炎症程度均明显减轻（P〈0．01），治疗后肝组织学活动指数改善率55．6％，门静脉炎症及纤维化程度无明显改善（P〉0．05）；治疗后血清HBVDNA水平明显下降（P〈0．01）；治疗后HBeAg血清转换率为50％（9／18）。结论：派罗欣治疗慢性乙肝可明显降低血清HBVDNA的水平，并改善肝组织的炎症及坏死程度，有利于肝功能的稳定。     

Is n-butyl-2-cyanoacrylate a biocompatible coating material for biodegradable fracture fixation devices? An experimental study on rats

The effect of n-butyl-2-cyanoacrylate monomer and polymer on the repair characteristics of cancellous bone was evaluated in an experimental study in which 105 male Wistar rats were operated on. A transverse drill channel 2mm in diameter and 5mm long in the femoral condyle was filled with a cylindrical implant of n-butyl-2-cyanoacrylate polymer or liquid n-butyl-2-cyanoacrylate monomer, which was polymerized in the tissue. The drill channel was left empty in the control group. Follow-up periods were one, three, six, 12, 24, 36 and 48 weeks. Radiographic, histologic, histomorphometric, oxytetracycline fluorescence and microradiographic studies were done. N-butyl-2-cyanoacrylate polymerdid not delaybone healing and was well tolerated by rat's cancellous bone tissue without signs of foreign body reaction or prolonged inflammation reaction. The polymerization of n-butyl-2-cyanoacrylate monomer caused the development of a narrow zone of bone necrosis or connective tissue around the implant depending on whether or not blood had interfered in the polymerization reaction. Bone necrosis and connective tissue worked as a biological and mechanical obstruction for bone healing towards the implant although there was no disturbance in the regenerative process in the trabecular network surrounding the implant.     

Multi-center clinical experience with a lumenless, catheter-delivered, bipolar, permanent pacemaker lead: implant safety and electrical performance

PURPOSE: Reduced lead diameter and reliability can be designed into transvenous permanent pacing leads through use of redundant insulation and removal of the stylet lumen. The model 3830 lead (Medtronic Inc., Minneapolis, MN, USA) is a bipolar, fixed-screw, steroid-eluting, lumenless, 4.1-Fr pacing lead. Implantation can be performed in a variety of right heart sites using a deflectable catheter (Model 10600, Medtronic). Lead performance and safety were studied. METHODS: Two prospective trials of 338 implanted subjects from 56 global sites were conducted. Electrical and safety data were obtained at implant, pre-discharge, and up to 18 months post-implant. Leads were implanted at traditional and alternate right heart sites. RESULTS: The study enrolled 338 subjects (204 males, 70.6 +/- 11.6 years) followed-up for a mean of 10.2 months (range, 0-21.6). Mean P-wave amplitudes ranged from 3.2 mV at 3 months to 2.9 mV at 18 months, while mean atrial pulse width thresholds at 2.5 V ranged from 0.07 ms at 3 months to 0.09 ms at 18 months. Mean R-wave amplitudes ranged from 11.3 mV to 11.1 mV and mean ventricular pulse width thresholds at 2.5 V ranged from 0.10 ms to 0.14 ms. There were 22 ventricular and 12 atrial lead complications within 3 months post-implant. Survival from lead-related complications improved to a clinically acceptable rate in the cohort of patients when revised implant techniques were employed. CONCLUSIONS: With the use of recommended implant techniques, the study results support the electrical efficacy and safety of a catheter-delivered, lumenless lead in traditional or alternate right atrium or right ventricle sites through 18 months post-implant.     

拉米夫定治疗慢性乙型肝炎的疗效及肝组织学改变

目的:观察拉米夫定治疗慢性乙型肝炎的临床疗效。方法:随机选择慢性乙型肝炎患者5 0例,给予口服拉米服定10 0 mg/ d,连用1a,动态观察服药0、6、12个月肝功能、HBV- DNA定量、血清肝纤维化指标透明质酸(HA)、层粘蛋白(L N)、型前胶原(P P)和 型胶原( C)的变化,对其中10例治疗前后行肝组织穿刺活检,观察肝脏组织学的改变。结果:与对照组相比,拉米夫定治疗组治疗后AL T、AST水平下降,HBV- DNA定量和4项血清肝纤维化指标均明显降低(P<0 .0 1)。肝细胞坏死、汇管区炎细胞浸润及纤维化明显减轻。结论:拉米夫定治疗慢性乙型肝炎,可以明显降低血清HBV- DNA及转氨酶水平,延缓肝组织纤维化的进展,减轻肝组织的炎症坏死。     

Cholic acid functionalized star poly(DL-lactide) for promoting cell adhesion and proliferation

Cholic acid functionalized star poly(DL-lactide) was synthesized through the ring-opening polymerization of DL-lactide initiated by cholic acid. The properties and cell behaviour of the cholic acid functionalized star poly(DL-lactide) were investigated as compared with linear poly(DL-lactide)s with different molecular weights and a star poly(DL-lactide) initiated by glycerol. In comparison to linear poly(DL-lactide)s, the cholic acid functionalized star poly(DL-lactide) had better wettability and slightly higher surface energy. The cell adhesion and proliferation on different materials were evaluated using two types of cells, 3T3 mouse fibroblasts and ECV304 human endothelial cells. Compared with the linear poly(DL-lactide)s, the cholic acid functionalized star poly(DL-lactide) showed obviously improved property for cell adhesion. The cell proliferation on the cholic acid functionalized star poly(DL-lactide) was also enhanced. The improvement in cell proliferation was not so significant as compared with the improvement in cell adhesion. This modification strategy provides an effective and simple way to promote cell attachment and growth in tissue engineering.     

Change in women's dietary fat intake following an acute cardiac event: Extent, predictors and comparison with non-cardiac Australian women and older adults.

BACKGROUND: Cardiac patients are encouraged to reduce their dietary fat intake, yet few studies have assessed fat intake in female cardiac patients. AIM: We assessed changes in fat intake for female cardiac patients at four occasions during the first year following their event, and compared it with fat intake for a non-cardiac sample. METHODS: The Short Fat Questionnaire (SFQ) was administered to 239 women aged 36 to 84 years consecutively admitted to four hospitals at the time of an acute event. Mplus was used to analyse change over time in SFQ scores and to identify predictors of change. Mean SFQ scores were compared with those for a sample of randomly selected Australian women and older adults. RESULTS: Mean SFQ scores decreased substantially during the first two months (t(139) = 8.374, p < 0.001), then increased over the subsequent 10 months (t(146) = 4.656, p < 0.001). By 12 months, SFQ scores remained significantly lower than at baseline. Older women and those with hypertension showed less reduction in fat intake. At all four time-points, mean SFQ scores were significantly lower than those reported for other Australian women and older adults. CONCLUSION: Even prior to their event, female cardiac patients reported lower fat intake than other Australian women and older adults, but showed partial deterioration in adherence following convalescence. Future studies could investigate options for assisting patients to sustain dietary changes, with attention to older patients and those with hypertension.     

Vascular and interstitial changes in the peritoneum of CAPD patients with peritoneal sclerosis.

OBJECTIVE: To analyze morphological changes in the peritoneum of peritoneal sclerosis (PS) patients. Emphasis was put on vascular abnormalities, because the continuous exposure to glucose-based dialysis solutions could cause diabetiform changes and because longitudinal transport studies suggested the development of a large peritoneal vascular surface area. DESIGN: Peritoneal biopsies from continuous ambulatory peritoneal dialysis (CAPD) patients were investigated in two studies. Diabetic patients were excluded. In study 1, 11 PS biopsies were compared to three control groups varying in duration of CAPD treatment: 0 months (n = 15), 2 - 25 months (n = 7), and > 25 months CAPD (n = 7). The second study was a case-control study, comparing six biopsies from the long-term control group to six PS biopsies, matched for age and duration of CAPD. All biopsies were scored for presence and type of fibrosis [Picro Sirius red, type IV collagen, alpha-smooth muscle actin (alphaSMA)] and for neoangiogenesis (factor VIII). Thickening of vascular walls by type IV collagen and vasodilation of capillaries were measured by computer-aided planimetry. RESULTS: In study 1 the presence of sclerosing fibrosis, deposition of interstitial type IV collagen, and the number of myofibroblasts (alphaSMA-positive cells) was greater in the PS biopsies than biopsies from all control groups (p < 0.002). Moreover, the number of vessels per field was higher in PS biopsies (p < 0.01). Vascular wall thickening of small arteries (p < 0.008) and vasodilation of capillaries were found in PS biopsies compared to all control groups (p < 0.007). The second study revealed differences in the presence of sclerosis but not in the extent of fibrosis between PS biopsies and their controls. The number of vessels per field in PS biopsies was higher compared to controls (p = 0.04). Also, thickening of the vascular wall was more marked in PS biopsies (p = 0.03). Vasodilation of capillaries was greater in PS biopsies than in controls (p = 0.07). CONCLUSION: Fibrosis of the peritoneum may precede peritoneal sclerosis. The deposition of type IV collagen and the presence of myofibroblasts in the interstitial layer could be part of a pathologic process similar to the scarring in diabetic nephropathy. Neoangiogenesis and thickening of the vascular wall by type IV collagen are consistent with glucose-induced microangiopathy.These abnormalities and the vasodilation of the capillaries can explain the high dialysate-to-plasma ratios or mass transfer area coefficients of low molecular weight solutes that can be found in long-term CAPD patients.     

股骨头表面置换对正常股骨头组织学的影响

背景:拟通过建立动物模型探讨目前的髋关节表面置换的假体设计是否达到成熟、是否能引起股骨头坏死。目的:观察健康新西兰大白兔股骨头表面置换后的组织形态变化。方法:60只健康大白兔行左股骨头表面置换,右侧为正常对照侧。分3,6,9,12周共4次分批处死取股骨头标本行大体、光镜、扫描电镜观察。结果与结论:股骨头表面置换后,股骨头骨质仅在与骨水泥接触界面(骨-水泥界面)有小范围的骨细胞坏死和肉芽组织增生纤维化、以及骨吸收;与金属假体接触的界面(骨-假体界面)亦有轻度小范围骨细胞坏死和肉芽组织增生纤维化,但无骨吸收表现;在远离骨水泥和假体的股骨头中心部位既无骨坏死表现,亦无骨吸收表现,组织表现与正常未手术骨质相同。结果可见股骨头表面置换不会引起正常股骨头的坏死,股骨头坏死与术式及假体本身无因果关系,在一定程度上肯定了表面置换治疗髋关节疾患的安全性和优越性。     

Concurrent delivery of dexamethasone and VEGF for localized inflammation control and angiogenesis.

Localized elution of corticosteroids has been used in suppressing inflammation and fibrosis associated with implantation and continuous in vivo residence of bio-medical devices. However, these agents also inhibit endogenous growth factors preventing angiogenesis at the local tissue, interface thereby delaying the healing process and negatively impacting device performance. In this work, a combination of dexamethasone and vascular endothelial growth factor (VEGF) was investigated for concurrent localized delivery using PLGA microsphere/PVA hydrogel composites. Pharmacodynamic effects were evaluated by histopathological examination of subcutaneous tissue surrounding implanted composites using a rat model. The hydrogel composites were capable of simultaneously releasing VEGF and dexamethasone with approximately zero order kinetics. Composites were successful in controlling the implant/tissue interface by suppressing inflammation and fibrosis as well as facilitating neo-angiogenesis at a fraction of their typical oral or i.v. bolus doses. Implants containing VEGF showed a significantly higher number of mature blood vessels at the end of the 4 week study irrespective of the presence of dexamethasone. Thus, localized concurrent elution of VEGF and dexamethasone can overcome the anti-angiogenic effects of the corticosteroid and can be used to engineer inflammation-free and well-vascularized tissue in the vicinity of the implant. These PLGA microsphere/PVA hydrogel composites show promise as coatings for implantable bio-medical devices to improve biocompatibility and ensure in vivo performance.     

In vitro-in vivo characterization of gentamicin bone implants.

A gentamicin carrier system composed of calcium phosphates, poly(DL-lactide) (PLA) and gentamicin was developed and characterized in vitro and in vivo for use in the prevention and treatment of bone infection. Four formulations were prepared according to an experimental design based on the Hadamard matrix. The technological variables included in the design were: gentamicin loading with respect to the implant weight, weight average molecular weight (M(w)) of the PLA as a compound of the matrix and the presence or absence of a PLA coating of 200 kDa. The variable to be optimized in vitro was the gentamicin release level during the first week. According to this goal, the selected formulation was F-D which was composed of 80% phosphates (25% hydroxyapatite, HAP and 75% tricalcium phosphate, TCP), 20% PLA (M(w), 30 kDa) and 3.5% gentamicin sulfate (GS) and was coated with PLA (M(w), 200 kDa). To elucidate the in vitro release mechanism of this implant, another implant lot (F-X) uncoated, but with identical matrix composition, was prepared. Results showed that the PLA coating delay the gentamicin release, indicating that part of the antibiotic released from the matrix diffuses through the polymer coating film. The selected formulation was tested in the femur of rabbits and showed a faster release rate in vivo than in vitro. This is due to a greater degree of PLA degradation, changes in the phosphate blend, and bone tissue invading the implant. Gentamicin concentration in the areas of the bone closest to the implant was higher than the minimum inhibitory concentration (MIC) against Staphylococcus aureus.     

Subcutaneous fat necrosis of the newborn

Subcutaneous fat necrosis (SCFN) is a rare fat tissue inflammation of the newborn. Risk factors include cord prolapse, perinatal asphyxia, therapeutic hypothermia, meconium aspiration, and sepsis. When present, hypercalcemia comes with lethargy, hypotonia, irritability, vomiting, polyuria, polydipsia, constipation, and dehydration. Kidney injury must be avoided. SCFN is often completely autoresolutive.     

大麻素受体1在慢性乙型肝炎患者肝组织表达及与血清转化生长因子-β1和瘦素的关系

目的 探讨大麻素受体1(CB1)在慢性乙型肝炎(CHB)患者肝组织中定位表达及其与肝纤维化评分、血清转化生长因子(TGF)-β1、瘦素(Leptin)水平的相关性.方法 选择118例CHB患者进行肝组织活检,通过免疫组织化学染色检测肝组织中CB1表达并进行CB1半定量评分.采用双抗体夹心ABC-ELISA法检测血清TGF-β1和keptin含量.据CB1表达量分为4组:(-)组、(+)组、(++)组、(+++)组.结果 随着肝组织CB1阳性表达量的不断增加,肝纤维化评分逐渐升高,各组间差异有统计学意义(F=23.369,P=0.000);血清TGF-β1和Leptin水平也逐渐升高,各组间差异有统计学意义(F值分别为8.762和5.749,P值分别为0.001和0.027).结论 CHB肝组织损伤可使肌纤维母细胞表达CB1增强,CB1可能通过与TGF-β1和kptin共同作用,诱导肝星状细胞的增殖、活化,导致肝纤 维化不断进展.

Abstract：

Objective To observe expression and location of cannabinoid receptor 1 (CB1) in liver tissue of patients with chronic hepatitis B (CHB) ,and analyze the relationship of it with the liver fibrosis score,the serum levels of TGF-β1 and Leptin. Methods Liver biopsies were performed in 118 patients with CHB.The expression of CB1 in liver tissue was observed by immune histochemical staining, and semi-quantitative analysis was carried out to devide the CB1 score into four grades: -, +, + +, + + +. Serum levels of TGF-β1 and Leptin were determined by ABC-ELISA double-antibody sandwich method. Results The expression of CB1 in liver tissue with CHB had significant relationship with the fibrosis score. As the expression of the CB1 increased, the fibrosis score became higher ( F = 23. 369,P = 0. 000). Moreover, the expression of CB1 in liver tissue with CHB had significant relationship with the serum levels of TGF-β1 and Leptin( F values were 8. 762 and 5. 749;P values were 0. 001 and 0. 027, respectively). Conclusion CB1 may play promotive role in the process of hepatic fibrosis through regulation of TGF-β1 and Leptin.     

Treatment of Wilson's disease with zinc. VI. Initial treatment studies

Eleven patients with newly diagnosed Wilson's disease were treated with zinc acetate as their sole anticopper therapy. Treatment duration was 8 to 37 months. Three of the patients had symptoms; in eight who were presymptomatic, diagnosis was made because of affected siblings who had symptoms. All patients did well clinically. Copper absorption was suppressed, as reflected by blockade of absorption of orally administered copper 64. Values for 24-hour urine copper and nonceruloplasmin plasma copper (freely available copper) were reduced. Values for liver-derived serum enzymes were also generally reduced in patients who had pretreatment elevations. Percutaneous liver biopsies were done initially and repeated in seven of the patients after 12 to 35 months of zinc therapy. In five of these patients a second biopsy specimen showed higher levels of copper than the first. In three of these five a third biopsy 6 to 23 months after the second revealed liver copper values that either had returned to the baseline value or were lower. One patient's initial biopsy specimen showed active inflammation, which subsided with therapy. All of the biopsies revealed histologic scarring typical of cirrhosis, and this did not appear to change over the course of therapy. We conclude that hepatic copper may increase temporarily during early zinc therapy but that the accumulated copper is sequestered in a nontoxic form. On the basis of animal studies we postulate that this sequestered copper is primarily bound to the high levels of hepatic metallothionein induced by zinc. Zinc appears to be a reasonable option for the initial treatment of patients with Wilson's disease, particularly those with presymptomatic disease.     

Acute pancreatitis masquerading as testicular torsion

A 40-year-old man presented with fat necrosis of scrotum as the complication of acute pancreatitis. Excessive fluid accumulation in the pancreas and the extrapancreatic spaces, including around the spermatic cord, was seen on computed tomography. Surgical specimen showed typical fat necrosis of tunica vaginalis and the spermatic cord. After the surgery, pain of the testicle subsided completely, without recurrence. From the clinical presentation alone, it had been difficult to differentiate this patient's condition from torsion of the spermatic cord.     

医患互动模式应用于糖尿病患者种植义齿修复后的效果

目的探讨医患互动模式应用于糖尿病患者种植义齿修复后的效果。方法便利抽样选取2014年11月至2016年3月在我院口腔门诊种植义齿修复后的糖尿病患者72例,按随机数字表法分成对照组和干预组各36例,对照组给予常规护理,干预组在常规护理的基础上行"3A+2P"医患互动。在义齿修复后1、3、6、12个月患者复诊时分别对两组患者糖代谢指标、种植义齿牙周指数指标、种植义齿存留率进行比较。结果两组患者在修复初期各项糖代谢指标差异均无统计学差异(均P0.05);重复测量的方差分析结果显示:两组干预时间与干预方法存在交互作用,不同组别随时间变化程度不同,干预组效果优于对照组,差异有统计学意义(均P0.05);在修复后12个月对两组患者种植义齿的存留率进行比较,差异有统计学意义(P0.05)。结论 "3A+2P"医患互动模式能保持糖尿病患者种植义齿修复后的糖代谢指标,维护种植义齿牙周健康,预防种植体周围炎的发生,延长种植义齿使用寿命,值得临床推广使用。     

自体脂肪注射移植隆乳术后并发症的超声特征

目的 探讨自体脂肪颗粒注射移植隆乳术后脂肪结节的超声图像特征及其演变过程,帮助临床与乳腺其他性质的肿块相鉴别.方法 对38例自体脂肪颗粒注射移植隆乳术患者进行术后超声随访,对超声发现的结节,描述结节的大小、部位、形态、边界、内部回声、钙化类型和声晕.结节每隔3～6个月随访,观察其大小及形态的变化.结果 38例中25例患者50侧乳房测及结节76个,其中实性16个(21.1%),囊实性8个(10.5%),囊性52个(68.4%).注射隆乳术后脂肪坏死结节的主要超声征象是无血流76个(100%),边界清晰66个(86.8%),形态规整54个(71.1%),无声晕74个(97.4%),囊性52个(68.4%),无钙化63个(82.9%),蛋壳样钙化10个(13.2%),囊实性结节中的实性成分随体位移动8个(100%).7例患者手术,病理诊断均为脂肪坏死.结论 超声监测自体脂肪颗粒注射移植隆乳术后并发症是一种有效的诊断方法,可减少不必要的盲目穿刺.     

The Speed of Sound in Rat Liver With Steatohepatitis: Ex Vivo Analysis Using Two Types of Ultrasound Systems

We have previously reported a non-invasive method that would be clinically applicable for measurement of speed of sound (SOS) in the liver. The objective of the present study was to confirm the utility of this new method for assessing over time the SOS in liver with progressive steatohepatitis of different grades and stages. Rats were divided into two groups—a control group and a steatohepatitis group—prepared by keeping the rats on a methionine and choline-deficient diet for 43 wk. The SOS through the liver tissue was measured using the new method in comparison with a pulse-receiver as the standard. The SOS through liver with steatohepatitis temporarily decreased with the fat deposition level and then increased in parallel with the progression of inflammation and fibrosis. Monitoring the change in SOS through liver tissue in individual patients with fatty liver would have considerable potential for assisting the non-invasive detection of early-stage steatohepatitis.     

Pathological features and prognosis in chronic hepatitis B virus carriers

This retrospective study examined 220 Chinese chronic hepatitis B virus carriers over 5 years. After initial liver biopsy, liver function tests and serological analysis, patients underwent further tests of liver function and hepatitis B seromarkers at 6-month intervals. Second and third liver biopsies were performed in 56 and 23 patients, respectively. Liver pathology was classified according to inflammatory activity (G(0) - G(4)) and degree of fibrosis (S(0) - S(4)). A significantly greater proportion of hepatitis B e antigen antibody-positive patients had a more severe level of inflammation and fibrosis than patients who were hepatitis B e antigen (HBeAg)-positive. Abnormal inflammation (≥ G(2)) occurred in 122 (55.5%) patients. Hepatitis B reactivation occurred in 35 (15.9%) patients: 33 had obvious liver inflammation at the initial biopsy (≥ G(2)) and only two had a low level of liver inflammation (G(0) - G(1)). The hepatitis B reactivation rate was significantly related to age but not to gender. Hepatitis B surface antigen clearance was 1.55% per year and HBeAg seroconversion was 5.36% per year. In conclusion, hepatitis B reactivation was closely correlated with age and the level of liver inflammation.     

Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages

Milk fat globule epidermal growth factor 8 (Mfge8) is a soluble glycoprotein known to regulate inflammation and immunity by mediating apoptotic cell clearance. Since fibrosis can occur as a result of exaggerated apoptosis and inflammation, we set out to investigate the hypothesis that Mfge8 might negatively regulate tissue fibrosis. We report here that Mfge8 does decrease the severity of tissue fibrosis in a mouse model of pulmonary fibrosis; however, it does so not through effects on inflammation and apoptotic cell clearance, but by binding and targeting collagen for cellular uptake through its discoidin domains. Initial analysis revealed that Mfge8^–/– mice exhibited enhanced pulmonary fibrosis after bleomycin-induced lung injury. However, they did not have increased inflammation or impaired apoptotic cell clearance after lung injury compared with Mfge8^+/+ mice; rather, they had a defect in collagen turnover. Further experiments indicated that Mfge8 directly bound collagen and that Mfge8^–/– macrophages exhibited defective collagen uptake that could be rescued by recombinant Mfge8 containing at least one discoidin domain. These data demonstrate a critical role for Mfge8 in decreasing the severity of murine tissue fibrosis by facilitating the removal of accumulated collagen.