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Biomedical subjects

M Entman

Publications and source records attributed to M Entman.

18 recordsLinked to original sources
PubMed2001

Matrix-dependent mechanism of neutrophil-mediated release and activation of matrix metalloproteinase 9 in myocardial ischemia/reperfusion.

BACKGROUND: A key component of reperfusion of myocardial infarction is an immediate inflammatory response, which enhances tissue repair. Matrix turnover is crucial to tissue repair, and matrix metalloproteinases (MMPs) are key enzymes involved in matrix degradation. The hypothesis tested is that one inflammation-based effector of tissue repair is the secretion and activation of MMP-9 by infiltrating neutrophils. METHODS AND RESULTS: Cardiac lymph and tissue were assayed for atent and active MMP-2 and MMP-9 by zymography and immunochemistry. Dual-labeling immunofluorescence determined the cellular source of MMP-9 protein. Isolated canine neutrophils were incubated with preischemic and postischemic cardiac lymph in the presence and absence of collagen-fibronectin pads, and the supernatants were assayed for latent and active MMP-9. MMP-9 increased during the first hours of reperfusion in both lymph supernatants and myocardial extracts, and this increase was of neutrophil origin. MMP-9 in the cardiac lymph remained latent but was activatable. In contrast, MMP-9 in the myocardium was in both latent and active forms. In situ zymography demonstrated that activated MMP-9 surrounded the infiltrated neutrophils. When postischemic cardiac lymph was incubated with neutrophils in vitro, MMP-9 secretion and activation occurred only in the presence of a collagen-fibronectin substrate; preischemic cardiac lymph did not induce significant secretion or activation. CONCLUSIONS: Infiltrating neutrophils are an early source of MMP-9 after reperfusion, and a portion of MMP-9 in the myocardium is active. Infiltrating neutrophils may localize MMP-9 activation by secreting MMP-9 and as a source of activating proteases.

Animals↗
PubMed2001

Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy.

BACKGROUND: -Hypertrophic cardiomyopathy (HCM), the most common cause of sudden cardiac death in the young, is characterized by cardiac hypertrophy, myocyte disarray, and interstitial fibrosis. We propose that hypertrophy and fibrosis are secondary to the activation of trophic and mitotic factors and, thus, potentially reversible. We determined whether the blockade of angiotensin II, a known cardiotrophic factor, could reverse or attenuate interstitial fibrosis in a transgenic mouse model of human HCM. METHODS AND RESULTS: We randomized 24 adult cardiac troponin T (cTnT-Q(92)) mice, which exhibit myocyte disarray and interstitial fibrosis, to treatment with losartan or placebo and included 12 nontransgenic mice as controls. The mean dose of losartan and the mean duration of therapy were 14.2+/-5.3 mg. kg(-1). d(-1) and 42+/-9.6 days, respectively. Mean age, number of males and females, and heart/body weight ratio were similar in the groups. Collagen volume fraction and extent of myocyte disarray were increased in the cTnT-Q(92) mice (placebo group) compared with nontransgenic mice (9.9+/-6.8% versus 4.5+/-2.2%, P=0.01, and 27.6+/-10.6% versus 3.9+/-2.3%, P<0.001, respectively). Treatment with losartan reduced collagen volume fraction by 49% to 4.9+/-2.9%. The expression of collagen 1alpha (I) and transforming growth factor-beta1, a mediator of angiotensin II profibrotic effect, were also reduced by 50%. Losartan had no effect on myocyte disarray. CONCLUSIONS: Treatment with losartan reversed interstitial fibrosis and the expression of collagen 1alpha (I) and transforming growth factor-beta1 in the hearts of cTnT-Q(92) mice. These findings suggest that losartan has the potential to reverse or attenuate interstitial fibrosis, a major predictor of sudden cardiac death, in human patients with HCM.

Angiotensin Receptor Antagonists↗
PubMed2000

Hydrogen peroxide induces LFA-1-dependent neutrophil adherence to cardiac myocytes.

Adult cardiac myocytes express intercellular adhesion molecule (ICAM)-1 in response to cytokine stimulation. This allows stable adhesion of chemotactically stimulated but not unstimulated neutrophils. In the current study, we demonstrated that brief exposure of ICAM-1-expressing cardiac myocytes to H(2)O(2) promoted transient adhesive interactions between myocytes and neutrophils without added chemotactic factors. This transient adhesion differed in two ways from the stable adhesion promoted by exogenous chemotactic factors. It occurred more rapidly, peaking within 15 min, and it was dependent on leukocyte function-associated antigen (LFA)-1 (CD11a/CD18) on the neutrophil interacting with ICAM-1 on the myocyte. In contrast, chemotactic factor-induced adhesion peaked at 60 min and was dependent on Mac-1 (CD11b/CD18). The transient adhesion could be completely inhibited by platelet-activating factor (PAF)-receptor antagonists WEB-2086 and SDZ-64-412. These results indicate that canine neutrophils may utilize both LFA-1 and Mac-1 to adhere to adult cardiac myocytes, with LFA-1 triggered by a PAF-like activity induced in myocytes by H(2)O(2).

Animals↗
PubMed1997

Prevention by anti-LFA-1 of acute myoblast death following transplantation.

Myoblast transplantation is a potential treatment for Duchenne muscular dystrophy. One of the problems possibly responsible for the limited success of clinical trials is the rapid death of the myoblasts after transplantation. To investigate this problem, myoblasts expressing beta-galactosidase were injected in the tibialis anterior muscles of mice. Beta-galactosidase activity was reduced by 74.7% after 3 days. Myoblast death observed at 3 days was reduced to 57.2% when the hosts were irradiated. This result suggested that host cells were contributing to this phenomenon. Transplantation in SCID and FK506-treated mice did not reduce cell death, indicating that mortality was not due to an acute specific reaction. In contrast, administration of the anti-LFA-1 (TIB-213) mAb markedly reduced myoblast death at 3 days without altering leukocyte tissue infiltration. We postulated that neutrophils were mediating myoblast mortality by an LFA-1-dependent mechanism. To test this hypothesis, IL-1beta-activated myoblasts were loaded with 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate, di(acetoxymethylester) (DCFH), a marker for oxidative stress. Addition of neutrophils and zymosan-activated serum resulted in a time-dependent DCFH fluorescence; this neutrophil-induced oxidation was considerably inhibited by TIB-213. These results indicate that an effective control of the inflammatory reaction will be necessary for any new clinical trials of myoblast transplantation and suggest that neutrophil-mediated myoblast injury occurs by an LFA-1-dependent pathway.

Animals↗
PubMed1997

Tumor necrosis factor-alpha provokes a hypertrophic growth response in adult cardiac myocytes.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine with a broad range of concentration-dependent effects. The recent observation that TNF-alpha is expressed by the cardiac myocyte after certain forms of stress suggests that TNF-alpha might contribute to the maintenance of normal tissue homeostasis after environmental injury. Accordingly, the purpose of this study was to examine the effects of TNF-alpha on protein synthesis in cultured adult cardiac myocytes. METHODS AND RESULTS: Cultured adult feline cardiac myocytes were stimulated with 10 to 1000 U/mL TNF-alpha to examine the effects of this cytokine on the rate of protein synthesis and degradation. Stimulation with TNF-alpha led to an accelerated rate of general protein synthesis and a time-dependent decrease in protein degradation in adult cardiac myocytes. The specificity of these findings was demonstrated by studies in which the effects of TNF-alpha on protein synthesis were blocked by a neutralizing anti-TNF-alpha antibody as well as studies in which TNF-alpha-conditioned medium had no effect on protein synthesis in myocytes. In addition to the TNF-alpha-induced increase in the general protein synthesis, stimulation with TNF-alpha led to a 2.4-fold increase in net actin protein synthesis and a 3.3-fold increase in net myosin heavy chain synthesis. Finally, the effects of TNF-alpha on adult cardiac myocytes were shown to be dependent on cell-substrate interaction, suggesting that the cell signaling pathways used by TNF-alpha are dependent on a preserved interaction between cell integrins and the extracellular matrix. CONCLUSIONS: The observation that TNF-alpha provokes a hypertrophic growth response in cardiac myocytes suggests that TNF-alpha may play an important role in myocardial homeostasis after environmental stress.

Actins↗
PubMed1993

Canine cardiac sarcoplasmic reticulum is not altered with endurance exercise training.

To investigate the effect of exercise training on calcium movements by isolated cardiac sarcoplasmic reticulum (SR), mongrel dogs either remained sedentary (S) or were exercise-trained (E) via running for a period of 8-10 wk. The trained state was confirmed by the increase in skeletal muscle citrate synthase activity and decreases in submaximal exercise heart rates in the E group but not in the S dogs. The properties of isolated cardiac SR were identical between the groups. The variables tested included ATP-dependent calcium transport and calcium-stimulated ATPase activity. Importantly, there was no difference in spontaneous calcium release which occurred after peak ATP-dependent calcium accumulation was reached. Calcium release from passively loaded vesicles induced by calcium and ionophore also did not differ in the SR isolated from the E dogs. The change in the affinity of the SR Ca ATPase for calcium after the addition of the polyanion, heparin, was similar in both groups, indicating that the regulation of calcium-stimulated ATPase activity by the SR protein, phospholamban, is not modified by exercise training. We conclude that exercise training of 8-10 wk duration does not alter the calcium handling properties of cardiac SR isolated from mongrel dogs.

Animals↗
PubMed1988

Acidosis-induced glucose intolerance is not prevented by adrenergic blockade.

The determinants of the altered glucoregulation in acidosis were investigated in anesthetized dogs. Because CO2 rapidly equilibrates and its effects are mediated by pH changes, CO2 inhalation was examined. Plasma acid-base composition, glucose, insulin, glucagon, and blood flows were evaluated before and after an intravenous glucose load (1.2 +/- 0.1 g/kg body wt) in normal and acidotic dogs with flow probes and catheters chronically implanted in the portal circulation. A simultaneous infusion of phentolamine (5 micrograms.kg-1.min-1), propranolol (3.5 micrograms.kg-1.min-1), both, or none was used. All acidemic dogs had lower hepatic extraction of insulin and greater hyperglycemia after the glucose challenge; thus the adrenergic system is not critical for these responses. Because arterial insulin levels were either normal (propranolol) or increased (all others) in acidosis, insulin resistance was likely. Insulin infusion (2 and 4 mU.kg-1.min-1) with euglycemic clamp and [3-3H]glucose documented that acidemia decreases peripheral glucose utilization and the insulin suppression of hepatic glucose production. Acidemia also enhances plasma glucagon levels, yet this effect plays a limited role in the observed hyperglycemia.

Acid-Base Equilibrium↗
PubMed1988

Endogenous opioids do not mediate HCl-induced myocardial dysfunction.

We evaluated the hypothesis that increased endogenous opioid activity mediates part or all of the left ventricular contractile and pump dysfunction previously demonstrated in HCl-induced metabolic acidemia. Eighteen Western newborn lambs were catheterized and instrumented; pacing wires were sutured to the right atrial appendage; a catheter mounted micromanometer pressure transducer was inserted into the left ventricle; and a 2.5 F thermistor was inserted into the distal abdominal aorta. The lambs were studied 3 days after surgery. Metabolic acidemia was produced with an infusion of 0.5 N HCl into the inferior vena cava. Inhibition of endogenous opioids was achieved with a bolus of 2 mg/kg of intravenous naloxone, which was demonstrated to inhibit morphine sulfate-induced myocardial dysfunction. The effects of opioid inhibition were contrasted with our previously published results after restoration of a normal arterial pH with intravenous sodium bicarbonate. In agreement with our previous study, we found that reducing the arterial pH from 7.41 +/- 0.01 to 6.97 +/- 0.04 was associated with a 45% reduction in cardiac output which resulted from a 50% reduction in stroke volume. These changes in turn were mediated by a 35% reduction in the maximal first derivative of left ventricular pressure and/or a 63% increase in systemic vascular resistance which we used to estimate contractility and afterload, respectively. Left ventricular end diastolic pressure increased during acidemia. Although opioid inhibition produced a consistent increase in the maximal first derivative of left ventricular pressure, this increase was relatively small and was not associated with a significant change in cardiac output, stroke volume, or systemic vascular resistance.

Acidosis↗
PubMed1986

Effects of alpha and beta adrenergic blockade on hepatic glucose balance before and after oral glucose. Role of insulin and glucagon.

In conscious dogs, phentolamine infusion significantly increased fasting portal vein insulin, glucagon, and decreased net hepatic glucose output and plasma glucose. Propranolol significantly decreased portal vein insulin, portal flow, and increased hepatic glucose production and plasma glucose. Phentolamine, propranolol, and combined blockade reduced glucose absorption after oral glucose. alpha, beta, and combined blockade abolished the augmented fractional hepatic insulin extraction after oral glucose. Despite different absolute amounts of glucose absorbed and different amounts of insulin reaching the liver, the percent of the absorbed glucose retained by the liver was similar for control and with alpha- or beta blockade, but markedly decreased with combined blockade. Our conclusions are: (a) phentolamine and propranolol effects on basal hepatic glucose production may predominantly reflect their action on insulin and glucagon secretion; (b) after oral glucose, alpha- and beta-blockers separately or combined decrease glucose release into the portal system; (c) net hepatic glucose uptake is predominantly determined by hyperglycemia but can be modulated by insulin and glucagon; (d) direct correlation does not exist between hepatic delivery and uptake of insulin and net hepatic glucose uptake; (e) alterations in oral glucose tolerance due to adrenergic blockers, beyond their effects on glucose absorption, can be, to a large extent, mediated by their effects on insulin and glucagon secretion reflecting both hepatic and peripheral glucose metabolism.

Administration, Oral↗
PubMed1985

Effects of atropine and gastric inhibitory polypeptide on hepatic glucose uptake and insulin extraction in conscious dogs.

Previous studies comparing the effects of oral, intraportal, and peripheral venous administration of glucose in conscious dogs demonstrated a significant increase in hepatic extraction of insulin only after oral glucose, but similar hepatic uptake of glucose after oral and intraportal glucose, which was greater than that after peripheral intravenous glucose infusion. This study evaluated the effect of atropine blockade of the parasympathetic nervous system on the increased fractional hepatic extraction of insulin and the role of gastric inhibitory polypeptide (GIP) on augmented hepatic uptake of oral glucose in conscious dogs with chronically implanted Doppler flow probes on the portal vein and hepatic artery, and catheters in the portal and hepatic veins and carotid artery. Since atropine infusion decreased absorption of glucose, and in order to achieve comparable portal vein levels of glucose and insulin, the dogs receiving atropine were given 1.9 +/- 0.1 g/kg glucose, compared with the control dogs who received 1.1 +/- 0.1 g/kg. The percentage of the glucose load that was absorbed was greater in the dogs not given atropine (80 +/- 4 vs. 44 +/- 7%), but because of the different loads, the absolute amount of glucose absorbed was similar in both groups (20.2 +/- 1.6 vs. 21.7 +/- 4.1 g). Although delayed by atropine, the peak portal vein glucose and insulin concentrations and the amounts presented to the liver were similar in both groups. However, the increased portal vein plasma flow and fractional hepatic extraction of insulin observed after oral glucose was not observed in the dogs infused with atropine. The net hepatic glucose uptake after oral glucose was significantly less at 10, 20, and 45 min in the atropine-treated dogs, and the area under the curve over the 180-min period was 44% less. However, the latter was not statistically significant. Infusion of GIP with peripheral intravenous glucose did not increase hepatic uptake of glucose or the fractional hepatic extraction of insulin compared with peripheral intravenous glucose alone. These results indicate an important role for parasympathetic innervation in the augmented fractional hepatic extraction of insulin, and increased portal vein plasma flow after oral glucose. Although a relationship between the augmented fractional extraction of insulin and the net hepatic glucose uptake may exist, it does not necessarily indicate that the former is required for the latter. Such parasympathetic innervation may be involved in the greater removal of glucose by the liver after oral compared with peripheral glucose administration. The augmented hepatic uptake of glucose and fractional hepatic extraction of insulin after oral glucose doesn not appear to be mediated by gastric inhibitory polypeptide.

Administration, Oral↗
PubMed1985

Effect of metabolic clearance rate and hepatic extraction of insulin on hepatic and peripheral contributions to hypoglycemia.

Effects of alterations in metabolic clearance rates, hepatic extraction, and plasma concentrations of insulin on hepatic and peripheral contribution to hypoglycemia and glucose counterregulation were studied in conscious dogs. Since insulin and sulfated insulin had markedly different metabolic clearance rates (34 +/- 1 vs. 16 +/- 1 ml/kg per min, respectively) and fractional hepatic extraction (42 +/- 1% vs. 15 +/- 2%, respectively), biologically equivalent amounts infused intraportally produced twofold higher hepatic vein and artery sulphated insulin concentrations and concentrations that were 30% higher in the portal vein. This significantly larger arterial/portal concentration ratio (0.67 vs. 0.45, respectively) permitted assessment of differential distribution of insulin on glucose turnover using [3-3H]glucose. Insulin and sulfated insulin (1 and 2 mU/kg per min) caused similar hypoglycemia. While insulin transiently suppressed glucose production and increased glucose disappearance, sulfated insulin had significantly greater effects on glucose disappearance and clearance, without suppression of glucose production. Despite similar hypoglycemia, sulfated insulin caused greater increment in glucagon. 3 mU/kg per min insulin caused more rapid and greater hypoglycemia, greater glucose clearance, and greater glucagon increments without suppression of glucose production, which indicates that with larger doses of insulin counterregulation can absolutely mask the suppressive effect of insulin. The effects of insulin and sulfated insulin were evaluated using euglycemic clamp to eliminate interference from stimulated counterregulation. Sequential infusion of 1 and 2 mU/kg per min of both insulins suppressed endogenous glucose production to 0 at 150 min, which indicates that the apparent lack of a hepatic effect of sulfated insulin during hypoglycemia was masked by greater counterregulation. This greater counterregulation may reflect greater peripheral glucose clearance, and prevented greater hypoglycemia than after the same insulin doses. The results indicate that the different rates of removal and the total metabolic clearance rate caused different concentrations and relative distribution between the portal and arterial blood compartments, leading to the significantly different contributions by the liver and peripheral tissues to the same hypoglycemia.

Animals↗
PubMed1983

The effect of ingestion of meat on hepatic extraction of insulin and glucagon and hepatic glucose output in conscious dogs.

The effect of ingestion of protein on hepatic extraction of insulin and glucagon and hepatic glucose output were investigated in conscious dogs. The ingestion of meat stimulated both insulin and glucagon secretion but the glucagon response was much more rapid and greater than that of insulin. Secretion of glucagon demonstrated a biphasic pattern while insulin release was monophasic. The fractional hepatic extraction of glucagon increased gradually from the basal value of 15 +/- 3% to a peak of 36 +/- 5% at 90 min, and that of insulin increased from the basal level of 41 +/- 2% to 54 +/- 4% at 45 and 60 min. The increased hepatic extraction of glucagon and insulin after meat ingestion may be explained by neural or hormonal signals from the gut. The blood glucose and hepatic glucose output did not increase significantly despite the significant decrease of the portal vein insulin to glucagon molar ratio as well as the significant decrease of the molar ratio of the hepatic uptake of these hormones. The absence of greater hepatic glucose production despite the augmented glucagon secretion and decreased portal vein insulin to glucagon molar ratio could reflect down regulation by glucagon.

Animals↗
PubMed1983

Absence of hepatic extraction of pancreatic polypeptide in conscious dogs.

In 15 conscious dogs basal portal vein pancreatic polypeptide (PP) (306 +/- 8 pg/ml) exceeded both hepatic vein PP (255 +/- 8 pg/ml) and arterial PP (244 +/- 9 pg/ml) and increased rapidly 10 min after oral glucose administration. In contrast to oral glucose, intraportal glucose infusion decreased PP levels from 45 min until the end of the infusion. Meat ingestion rapidly and promptly increased PP. During the basal state, hepatic extraction of total immunoreactive PP was 10 +/- 4%, not significantly different from zero, of the 150 +/- 14 ng/min presented to the liver. Fractional hepatic extraction of PP did not change after oral glucose, meat ingestion, or intraportal glucose infusion. Chromatographic analysis showed at least four different components of immunoreactive PP. The first peak eluted with the void volume, the second peak between the void volume and authentic PP, and the third peak coincided with authentic PP. When present, the fourth peak eluted after authentic PP. More than half of the immunoreactive PP in the basal state eluted with authentic PP, whereas about one-third was found in the second peak. The marked alterations in PP after meat, oral glucose, or intraportal glucose and atropine reflected primarily changes in the third peak. The fractional hepatic extraction of all the components was very similar.

Animals↗
PubMed1983

Differential effects of oral, peripheral intravenous, and intraportal glucose on hepatic glucose uptake and insulin and glucagon extraction in conscious dogs.

The effect of equal (1.1 +/- 0.1 g/kg body wt) amounts of glucose administered orally, or by peripheral intravenous or intraportal infusion on hepatic glucose uptake and fractional hepatic extraction of insulin and glucagon was studied in conscious dogs with chronically implanted Doppler flow probes on the portal vein and hepatic artery and catheters in the portal vein, hepatic vein, carotid artery, and superior mesenteric vein. Portal vein and hepatic vein plasma flow increased only after oral glucose administration. Arterial plasma glucose increased equally to 150-160 mg/100 ml after all three routes of glucose administration. Portal vein glucose was similar after oral (195 +/- 15 mg/100 ml) and intraportal glucose infusion (215 +/- 11 mg/100 ml) and significantly higher than after peripheral intravenous glucose. Hepatic glucose uptake after oral (68 +/- 4%) and intraportal glucose administration (65 +/- 7%) significantly exceeded that after peripheral intravenous glucose infusion (23 +/- 5%). The amount of insulin above basal presented to the liver during the 180 min after oral glucose was 7.6 +/- 1.3 U, 4.3 +/- 0.6 U after intraportal glucose, and 4.1 +/- 0.6 U after peripheral intravenous glucose. Hepatic extraction of insulin increased significantly after oral glucose (42 +/- 3 to 61 +/- 4%), but was unchanged after intraportal and peripheral intravenous glucose administration. When the portal vein glucose levels achieved during peripheral intravenous glucose infusion for 90 min were maintained by a subsequent 90-min intraportal glucose infusion, hepatic glucose uptake was significantly greater during the intraportal glucose infusion. Glucagon secretion was suppressed equally after oral glucose, intraportal glucose, and peripheral intravenous glucose administration; fractional hepatic extraction of that hormone, which was significantly less than that of insulin, was unchanged. These results indicate that hepatic glucose uptake is significantly greater after oral and intraportal glucose administration than after peripheral intravenous glucose infusion. This difference is not simply related to the amount of glucose or insulin presented to the liver and the increased hepatic glucose uptake did not depend solely upon the augmented fractional hepatic extraction of insulin. Hepatic extraction of insulin and hepatic glucose uptake appear to be regulated independently.

Administration, Oral↗
PubMed1981

The effect of tolbutamide and hepatic extraction of insulin and glucagon and hepatic glucose output in anesthetized dogs.

The effects of tolbutamide and insulin infusion on hepatic extraction of insulin and glucagon and on hepatic glucose output were compared in anesthetized dogs. The basal hepatic extraction of insulin was not significantly different in the two experiments (62 +/- 7% vs. 49 +/- 8%). The fraction of insulin extracted by the liver was not changed by either tolbutamide or insulin administration. In contrast, hepatic extraction of glucagon significantly increased from a basal value of 12 +/- 8% to 41 +/- 12% 30 min after tolbutamide, coincident with hypoglycemia and increased secretion of glucagon. The percent hepatic extraction of glucagon did not change during insulin infusion despite similar hypoglycemia and an even greater increase in the amount of glucagon reaching the liver. Tolbutamide and insulin produced a transient fall in hepatic glucose output which was associated with a significant increase in the insulin to glucagon molar ratio of the portal vein. Despite the persistence of hypoglycemia, hepatic glucose production returned to control values, and the portal venous insulin to glucagon molar ratio returned toward normal. Thus, the initial hypoglycemia after tolbutamide and insulin treatment reflects decreased hepatic glucose production, while the later effects represent increased peripheral glucose utilization. Hepatic glucose output correlated better with the portal venous insulin to glucagon molar ratio than the ratio of the hormones removed by the liver. These findings indicate that insulin and glucagon extraction by the liver are quite different and are independently regulated. Tolbutamide directly increases the fraction of glucagon removed by the liver. Because of changes in hepatic extraction after tolbutamide, increased pancreatic secretion of glucagon might not be reflected in its peripheral concentration.

Animals↗
PubMedDate not supplied

Control of inflammatory damage by anti-LFA-1: increase success of myoblast transplantation.

Myoblast transplantation is a potential treatment for Duchenne Muscular Dystrophy. This article confirms by experiments in mice that one problem that has limited the success of clinical trials of this procedure is a rapid (within 3 days) inflammatory reaction which kills most of the injected myoblasts. The death of the transplanted myoblasts can be prevented by treating the host with a mAb against LFA-1. This led to a 27-fold increase in the number of muscle fibers expressing a reporter gene present in the donor myoblasts when the host is also adequately immunosuppressed with FK506. Therefore, both the nonspecific inflammatory reaction and the specific immune response should be adequately controlled following myoblast transplantation.

Animals↗