Biomedical subjects

A Martino

Publications and source records attributed to A Martino.

At least 19 recordsLinked to original sources

PubMed2007

Sphingosine 1-phosphate interferes on the differentiation of human monocytes into competent dendritic cells.

Sphingosine 1-phosphate (S1P) is a lipidic messenger known to exert several physiological functions within the cell. We tested here whether the stimulation of human monocytes with different doses of S1P might interfere with their differentiation into competent dendritic cells (DC). Monocytes cultured with granulocyte macrophage colony stimulating factor, interleukin-4 (IL-4) and S1P differentiated into a DC population lacking CD1a molecules on the surface and acquired some aspects of mature DC (mDC), though in the absence of maturation stimuli. When stimulated with lipopolisaccharide (LPS), CD1a(-) DC produce high amounts of tumour necrosis factor-alpha and IL-10, but not IL-12. Accordingly, these CD1a(-) DC were not capable of stimulating allogenic T lymphocytes so well as CD1a(+) DC generated from untreated monocytes and maturated with LPS. S1P monocyte-derived DC lost their polarizing capacity abrogating the production of gamma-interferon/IL-4 by co-cultured naïve CD4(+)CD45RA(+) T cells. Our findings suggest a mechanism through which S1P can favour the development of immune-related pathological states.

Antigens, CD1↗

PubMed2006

Kinking, coiling, and tortuosity of extracranial internal carotid artery: is it the effect of a metaplasia?

INTRODUCTION: Morphological anomalies of the extracranial internal carotid artery (ICA) cause symptomatic cerebrovascular insufficiency in 4-16% of the cases. The aim of the present study is to evaluate macroscopic and microscopic features of a group of extracranial ICA anomalies, specifically kinking, coiling, and tortuosity, eventually affecting the surgical approach. MATERIALS AND METHODS: From January 2003 to December 2005, 10 out of 169 (6%) revascularized patients (pts) were operated upon because of an ICA anomaly. They were all but two symptomatics. Seven pts were treated by ICA transection and end-to-side reimplantation of the ICA at the level of the carotid bulb; three pts were treated by ICA resection and end-to-end anastomosis. In all the cases a segment of ICA was resected; in three cases one more segment was also obtained from a common carotid artery (CCA) and these specimens were histologically examined. Patients were followed-up through a 3-year period. RESULTS: No pts died and none suffered of neurologic events. Duplex scan and arteriographic postoperative control showed the correct surgical reconstruction. Matching preoperative clinical findings with presence or absence of significant atherosclerotic stenotic lesion, we found out a positive cerebral CT in one pt (20%) in both groups; fluent neurological deficit was preeminent in pts with pure ICA anomalies (40% vs. 0%) (P = 0.2); pts with pure ICA anomalies were significantly younger than 65 years old (80% vs. 0%) (P = 0.03) and males were more involved by pure ICA anomalies (60% vs. 40%) (P = 0.1). The histological examination of ICA specimens showed a reduction of elastic fibers and muscular cells with a compensative increase of connective fibers. CONCLUSIONS: At our knowledge this is the first study focused on ICA anomalies like kinking, coiling, and tortuosity, comparing histologic features of CCA and ICA specimens coming from the same affected carotid axis. Our results, although preliminary, show elastic and muscular tissue substituted by loose connective tissue, configuring a metaplasia of tunica media limited to the ICA. Our hypothesis is that extracranial ICA, being a segment of transition between an elastic vessel (CCA) and a muscular vessel (intracranial ICA), is particularly subject to metaplastic transformation, analogously to other transition zones in human body. Our purpose is now to confirm by ultrastructural and molecular biology techniques, in a wider series, the presence of this metaplasia, since this could condition also the revascularization techniques.

Age Factors↗

PubMed2006

High accuracy and cost-effectiveness of a biopsy-avoiding endoscopic approach in diagnosing coeliac disease.

BACKGROUND: The 'immersion' technique during upper endoscopy allows the visualization of duodenal villi and the detection of total villous atrophy. AIM: To evaluate the accuracy of the immersion technique in detecting total villous atrophy in suspected coeliac patients. The accuracy in diagnosing coeliac disease and the potential cost-sparing of a biopsy-avoiding approach, based on selection of individuals with coeliac disease-related antibodies and on endoscopic detection of absence of villi, were also analysed. METHODS: The immersion technique was performed in 79 patients with positive antibodies and in 105 controls. Duodenal villi were evaluated as present or absent. As reference, results were compared with histology. Diagnostic approaches, including endoscopy with or without biopsy, were designed to investigate patients with coeliac disease-related antibodies and total villous atrophy. A cost-minimization analysis was performed. RESULTS: All patients with positive antibodies had coeliac disease. The sensitivity, specificity, positive and negative predictive values of endoscopy to detect total villous atrophy was always 100%. The sensitivity, specificity, positive and negative predictive values of biopsy-avoiding or biopsy-including strategies in diagnosing coeliac disease when villi were absent was always 100%. The biopsy-avoiding strategy was cost-sparing. CONCLUSIONS: Upper endoscopy is highly accurate in detecting total villous atrophy coeliac patients. A biopsy-avoiding approach is both accurate and cost-sparing to diagnose coeliac disease in subjects with marked duodenal villous atrophy.

Adolescent↗

PubMed2005

The effects of GnRH treatment at the time of AI and 12 days later on reproductive performance of high producing dairy cows during the warm season in northeastern Spain.

It was hypothesized that gonadotropin-releasing hormone (GnRH) treatment at the time of insemination and 12 days later increases conception rates. The aim of the present study was to evaluate the effects of GnRH treatment at the time of insemination or at the time of insemination and 12 days later on reproductive performance during the warm season in high producing dairy cows. The effect of GnRH treatment on the incidence of subsequent twin pregnancies and pregnancy losses was also evaluated. Data were analyzed using logistic regression methods. Of the entire series of 1289 AI, 373 (29%) resulted in pregnancy. Three study groups were established to evaluate the effects of treatment on the conception rate: control (untreated cows, n=431), GnRH-0 (cows receiving GnRH at AI, n=429) or GnRH-0+12 (cows receiving GnRH at AI and at AI+12 days, n=429). Conception rates were 20.6% (89/431), 30.8% (132/429) and 35.4% (152/429) for animals receiving no treatment, GnRH at AI, and GnRH at AI and 12 days later, respectively. Based on the odds ratio, the probability of pregnancy was 0.80 and 0.46 times less likely for cows receiving treatment GnRH-0 and no treatment, respectively, than for cows receiving treatment GnRH-0+12 (reference). Of the 373 pregnant animals, 326 (87.4%) bore singletons and 47 (12.6%) carried twins. The effects of treatment on the dependent variables: twin pregnancy, additional corpus luteum and pregnancy loss were analyzed. Pregnancy loss between 38 and 90 days after insemination was registered in 30 (8%) cows: 17 (5.2%) in single and 13 (27.7%) in twin pregnancies. Fifty-six (15%) cows had an additional corpus luteum. No pregnancy losses were recorded in these cows. Treatment had no effect on the twin pregnancy rate. The treatment GnRH at AI and 12 days later increased the chances of an additional corpus luteum by a factor 3.7 (using the control group as reference). In conclusion, our results support the hypothesis that GnRH treatment at the time of insemination and 12 days later increases the conception rate in high producing dairy cows during the warm season. Although lower than double treatment, strong benefits were also registered following a single GnRH treatment at insemination. Under these conditions, treatment fails to affect the twin pregnancy rate yet increases the incidence of an additional corpus luteum in pregnant cows.

Abortion, Veterinary↗

PubMed2004

High efficacy of 1-week doxycycline- and amoxicillin-based quadruple regimen in a culture-guided, third-line treatment approach for Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori infection may persist after both first- and second-line current treatments. AIM: To assess the efficacy of a third-line, culture-guided treatment approach for the eradication of H. pylori. METHODS: Patterns of resistance were analysed in H. pylori isolates from 94 consecutive patients in whom H. pylori infection had persisted after two eradication attempts. Using the epsilometer test, susceptibility analysis was performed for amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin. Patients were then treated with a culture-guided, third-line regimen: 89 patients with a 1-week quadruple regimen including omeprazole, bismuth, doxycycline and amoxicillin, and five patients with a 1-week triple regimen containing omeprazole, amoxicillin and levofloxacin or clarithromycin. RESULTS: Ninety-four subjects (100%) were resistant to metronidazole, 89 (95%) to clarithromycin, 29 (31%) to levofloxacin and five (5%) to tetracycline. No resistance to amoxicillin was found in any patient. Overall, H. pylori eradication was obtained in 90% of subjects. The quadruple regimen was effective in 81 patients (92% by per protocol and 91% by intention-to-treat analysis). Four patients (80%, both per protocol and intention-to-treat analysis) were H. pylori-negative after the triple regimen. CONCLUSIONS: A culture-guided, third-line therapeutic approach is effective for the eradication of H. pylori. Furthermore, the 1-week doxycycline- and amoxicillin-based quadruple regimen is a good third-line 'rescue' treatment option.

Amoxicillin↗

PubMed2004

Comet assay and micronucleus test in circulating erythrocytes of Cyprinus carpio specimens exposed in situ to lake waters treated with disinfectants for potabilization.

The detection of a possible genotoxic effect of surface water treated with disinfectants for potabilization is the aim of the present work. The Comet assay and the micronucleus test were applied in circulating erythrocytes of Cyprinus carpio. Young specimens (20-30 g) were exposed in experimental basins, built within the potabilization plant of Castiglione del Lago (Perugia, Italy). In this plant the water of the Trasimeno Lake is treated and disinfected for potabilization before it is distributed to the people in the net of drinkable water. A continuous flow of water at a constant rate was supplied to basins; the water was continuously treated at a constant concentration with one of the three tested disinfectants (sodium hypochlorite, peracetic acid and chloride dioxide), one control basin being supplied with untreated water. Three sampling campaigns were performed: October 2000, February 2001 and June 2001. Repeated blood samplings through intracardiac punctures allowed to follow the same fish populations after different exposure times: before introduction of the disinfectant, and 10 or 20 days afterwards. An additional blood sampling was performed 3 h after addition of the disinfectant in other, simultaneously exposed, fish populations. Genotoxic damage was shown in fish exposed to water disinfected with sodium hypochlorite and chloride dioxide. The Comet assay showed an immediate response, i.e. DNA damage that was induced directly in circulating erythrocytes, whereas micronuclei reached their highest frequencies at later sampling times, when a genotoxic damage in stem cells of the cephalic kidney is expressed in circulating erythrocytes. The quality of the untreated surface water seems to be the most important parameter for the long-term DNA damage in circulating erythrocytes.

Animals↗

PubMed2004

High prevalence of hyperplastic colonic polyps in acromegalic subjects.

We evaluated the prevalence and features of colonic polyps in a population of acromegalic subjects, compared to a control group of patients with irritable bowel syndrome (IBS). Colonic polyps were found in 30 acromegalic subjects (40%) and in 10 controls (13%) (P < 0.0001). Among the acromegalic patients, polyps were of the hyperplastic type in 27 subjects (90%) and adenomatous in 3 (10%). In the control group, polyps were hyperplastic in nine subjects (90%) and adenomatous in one (10%). We also observed a significant association (P < 0.0001) between the presence of hyperplastic polyps and the older age in both the acromegalic and the control groups. There were no differences between the two groups regarding sex, site, size, or macroscopic and histological types of polyps. Acromegalic patients have a higher prevalence of colonic hyperplastic polyps than IBS subjects, while the prevalence of adenomatous polyps is similar in the two groups.

Acromegaly↗

PubMed2003

Role of macrophage phospholipase D in natural and CpG-induced antimycobacterial activity.

The present study addresses the differential ability of macrophages to control intracellular growth of non-pathogenic Mycobacterium smegmatis (Msm) and pathogenic M. tuberculosis (MTB). Results reported herein show that 3 h post infection, intracellular Msm, but not MTB, was significantly killed by macrophages. As the role of human macrophage phospholipase D (PLD) in the activation of antimicrobial mechanisms has been documented, we hypothesised the role of such enzyme in antimycobacterial mechanisms. To this aim, macrophage PLD activity was analysed at different times after exposure with either pathogenic MTB or non-pathogenic Msm. Results showed that, starting from 15 min after mycobacterial exposure, MTB did not induce macrophage PLD activity, whereas the environmental non-pathogenic Msm stably increased it. The direct contribution of PLD in intracellular mycobacterial killing was also analysed by inhibiting enzymatic activity with ethanol or calphostin C. Results show that PLD inhibition significantly increases intracellular Msm replication. In order to see whether the innate PLD-mediated antimicrobial mechanisms against MTB are also induced after CpG ODN stimulation, the role of PLD has been analysed in the course of CpG-mediated intracellular MTB killing. CpG DNA increased PLD activity in both uninfected and MTB-infected macrophages, and the inhibition of PLD activity resulted in a significant reduction of CpG-induced MTB killing. Taken together, our data suggest a relationship between host PLD activation and the macrophage ability to control intracellular mycobacterial growth.

Cell Line↗

PubMed2003

Differential sensitivity of human monocytes and macrophages to ANP: a role of intracellular pH on reactive oxygen species production through the phospholipase involvement.

Atrial natriuretic peptide (ANP), a cardiovascular hormone, elicits different biological actions in the immune system. The aim of the present work was to study the effect of ANP on the intracellular pH (pHi) of human monocytes and macrophages and to investigate whether pHi changes could play a role on phospholipase activities and reactive oxygen species (ROS) production. Human macrophages isolated by peripheral blood mononuclear cells and THP-1 monocytes, which were shown to express all three natriuretic peptide receptors (NPR-A, NPR-B, and NPR-C), were treated with physiological concentrations of ANP. A significant decrease of pHi was observed in ANP-treated macrophages with respect to untreated cells; this effect was paralleled by enhanced phospholipase activity and ROS production. Moreover, all assessed ANP effects seem to be mediated by the NPR-C. In contrast, no significant effect on pHi was observed in THP-1 monocytes treated with ANP. Treatment of macrophages or THP-1 monocytes with 5-(N-ethyl-N-isopropyl)amiloride, a specific Na(+)/H(+) antiport inhibitor, decreases pHi in macrophages and monocytes. Our results indicate that only macrophages respond to ANP in terms of pHi and ROS production, through diacylglycerol and phosphatidic acid involvement, pointing to ANP as a new modulator of ROS production in macrophages.

Amiloride↗

PubMed2002

Proinflammatory cytokines in the course of Mycobacterium tuberculosis-induced apoptosis in monocytes/macrophages.

Mycobacterium tuberculosis (MTB) can induce apoptosis in monocytes/macrophages both in vitro and in vivo, and this phenomenon is associated with mycobacterial survival. The present study addresses the possibility that apoptotic and inflammatory pathways could coexist through a caspase-1-mediated mechanism. In this context, a caspase-1 inhibitor (YVAD), but not caspase-3 (DEVD) or caspase-4 (LEVD) inhibitors, was able to strongly inhibit MTB-induced apoptosis. Moreover, caspase-1 activity was confirmed by the increased maturation of interleukin (IL)-1beta. Of interest, IL-1beta and tumor necrosis factor (TNF)-alpha were produced massively in the course of infection, and both were inhibited by YVAD pretreatment. To determine whether TNF-alpha was produced actively by apoptotic cells, the intracytoplasmatic cytokine content and apoptotic phenotype were analyzed at the single-cell level. Results showed a progressive increase of TNF-alpha production in annexin V-positive cells. These results indicate that MTB-induced apoptosis is associated with proinflammatory cytokine production.

Apoptosis↗

PubMed2002

Italian multicenter survey on laparoscopic treatment of gastro-esophageal reflux disease in children.

BACKGROUND: Skepticism is still present today about the laparoscopic treatment of gastro-esophageal reflux (GER) in children. We present the prospective experience and short-term results of eight Italian pediatric surgical units. METHODS: We included all the children with complicated GER, operated after January 1998 by single surgeons from eight different centers. Diagnostic aspects, type of fundoplication, and complications were considered. All the patients were followed for a minimum period of 6 months in order to detect complications or recurrences. RESULTS: 288 children were prospectively included. Mean age was 4.8 years (3 m-14 y). Nissen fundoplication was done in 25%, floppy Nissen in 63%, Toupet in 1.7%, and anterior procedures (Lortat Jacob, Thal) in 10%. Gastrostomy was associated, if neurological impairment or feeding disorders were present. Mean follow-up was 15 months and reoperation was necessary in 3.8% of cases. CONCLUSIONS: This experience underlines that minimal invasive access surgery in children is safe and that the laparoscopic approach is considered in eight centers the golden standard for surgical repair of gastro-esophageal reflux disease maintaining the same indications and techniques of the open approach.

Adolescent↗

PubMed2002

Digestive hemorrhages of obscure origin.

BACKGROUND: The diagnosis of digestive bleeding in some cases can require a diagnostic laparotomy when other methods have been ineffective. Video-laparoscopy can provide such cases with a certain diagnosis and the possibility of performing a simultaneous surgical treatment. METHODS: Our experience using video-laparoscopic to treat digestive hemorrhages of obscure origin involved 16 patients. The examined patients presented with the following diseases: Meckel's diverticulum (8 cases), gastric leiomyoma (1 case), small bowel leiomyoma (4 cases), jejunum leiomyosarcoma (1 case), small bowel melanoma (1 case), and Peutz-Jeghers syndrome (1 case). RESULTS: In all these patients the laparoscopic approach allowed us to identify the origin and site of the hemorrhages, and subsequently to treat the identified lesions. In one patient, an intraperitoneal resection of the diverticulum was performed using Endo-Gia (TM30NIF; Tyco Auto-Suture). In the remaining cases, a minilaparatomy was performed for resection of the disordered loop. CONCLUSIONS: Video-laparoscopy is very useful for avoiding explorative laparatomies on patients affected by digestive hemorrhages of obscure origin. In these cases, the video-laparoscopic approach allows full and meticulous explorations of the small bowel to be performed, and seems to be useful for diagnosis through direct observation of the lesions. Moreover, if necessary, video-laparoscopy can be used for the effective treatment of the diseases.

Adolescent↗

PubMed2002

[Vascular ligation for severe obstetrical hemorrhage: review of the literature].

OBJECTIVE: Assess the contribution of vascular ligation in the treatment of severe obstetrical hemorrhage. Method. We reviewed the anatomic and pathophysiological basis of vascular ligation analyzing the technique, results, and indications for this conservative procedure for the severe post-partum hemorrhage. New developments in suture techniques for uterine bleeding are under study. RESULTS: Outcome after uterine artery ligation is good. A stepwise procedure with progressive ligation of the uterine and ovarian arteries is a good solution (100% success). Bilateral ligation of the hypogastrics can provide success in 66% of cases. Vascular ligation can be an alternative between embolization and hysterectomy. CONCLUSION: Ligation of the bleeding vessels preserves the patient's life and uterus. More than fifty pregnancies have been reported after vascular ligation.

Arteries↗

PubMed2001

Stat5 and Sp1 regulate transcription of the cyclin D2 gene in response to IL-2.

The IL-2R promotes rapid expansion of activated T cells through signals mediated by the adaptor protein Shc and the transcription factor Stat5. The mechanisms that engage the cell cycle are not well defined. We report on the transcriptional regulation of the cell cycle gene cyclin D2 by the IL-2R. IL-2-responsive induction of a luciferase reporter gene containing 1624 bp of the cyclin D2 promoter/enhancer was studied in the murine CD8(+) T cell line CTLL2. Reporter gene deletional analysis and EMSAs indicate an IL-2-regulated enhancer element flanks nucleotide -1204 and binds a complex of at least three proteins. The enhancer element is bound constitutively by Sp1 and an unknown factor(s) and inducibly by Stat5 in response to IL-2. The Stat5 binding site was essential for IL-2-mediated reporter gene activity, and maximum induction required the adjacent Sp1 binding site. Receptor mutagenesis studies in the pro-B cell line BA/FG (a derivative of the BA/F3 cell line) demonstrated a correlation between Stat5 activity and cyclin D2 mRNA levels when the Stat5 signal was isolated, disrupted, and then rescued. Further, a dominant-negative form of Stat5 lacking the trans-activation domain inhibited induction of cyclin D2 mRNA. We propose that the IL-2R regulates the cyclin D2 gene in part through formation of an enhancer complex containing Stat5 and Sp1.

5' Untranslated Regions↗

PubMed2001

Transthoracic and transesophageal echocardiographic indices predictive of sinus rhythm maintenance after cardioversion of atrial fibrillation: an echocardiographic study during direct current shock.

BACKGROUND: Up to 57% of atrial fibrillation (AF) recurrences after cardioversion take place during the first 30 days following direct current shock (DCS) delivery. Previous echocardiographic studies on sinus rhythm (SR) maintenance after cardioversion have focused mainly on parameters recorded before DCS, while other studies have reported on the indices recorded soon after delivery of the shock. METHODS: Therefore, we investigated 18 patients with nonrheumatic AF, selected to undergo DCS, by both transthoracic (TTE) and transesophageal (TEE) echocardiography performed within 10 minutes before and after the electrical shock delivery. TTE was utilized for the evaluation of left atrium and left ventricle shape as well as for mitral Doppler flow sampling, while TEE was used to evaluate left atrial appendage (LAA) morphology and function, to score the LAA spontaneous echo contrast, and to evaluate the flow of left superior pulmonary vein; the transesophageal probe was left in situ during the electrical procedure. Thirty days after cardioversion, 10 (55%) patients maintained SR (Group 1) while 8 (45%) reverted to AF (Group 2). We compared the mean values of the parameters recorded in the two groups both before and after DCS. RESULTS: Although many parameters of pre- and postcardioversion analysis proved to be significantly different between the two groups, the most marked differences were exhibited by the following postcardioversion indices: Peak Doppler flow velocity of the end-diastolic mitral flow (30.10 +/- 5.24 vs. 20.50 +/- 6.32 cm/sec, P = 0.003); sum of peak velocities of the end-diastolic contraction (A) and relaxation (A(1)) of LAA (A + A(1) = 58.20 +/- 17.02 vs. 31.25 +/- 9.27 cm/sec, P = 0.001); duration of A + A(1) (162.70 +/- 27.01 vs. 133.75 +/- 5.31 msec, P = 0.002); and sum of durations of the early diastolic forward (E) and reverse (E(1)) flow of LAA (101.90 +/- 35.15 vs. 53.33 +/- 16.33 msec, P = 0.006). CONCLUSIONS: Using a single echocardiographic examination during DCS and after induction of anesthesia, without further discomfort to patients, we were able to identify useful parameters for the prediction of future electrical activity of the heart before as well as soon after DCS. Postcardioversion indices, derived by both TTE and TEE, were even more predictive of SR maintenance after 1 month than precardioversion parameters.

Adult↗

PubMed2001

One-trocar surgery: a less invasive videosurgical approach in childhood.

BACKGROUND/PURPOSE: Laparoscopic techniques and instruments are evolving to lessen the invasiveness of this surgical approach. The authors present their experience with the videosurgical approach using only 1 trocar. METHODS: Between October 1997 and January 2000 the authors performed 59 videosurgical procedures using a 1-trocar approach (mean age, 11.5 years; range, 4 to 18 years). A 10-mm Hasson trocar was inserted in an "open" fashion either through the umbilicus (laparoscopy) or below the apex of the 12th rib (retroperitoneoscopy). An operative laparoscope was used in all cases. The operations were 18 retroperitoneoscopic Palomo varicocelectomies, 1 retroperitoneoscopic renal biopsy, 38 appendectomies, and 2 ileal resections (Meckel's diverticulum, duplication cyst). For appendectomies and ileal resections, the corresponding intestinal loop was grasped and exteriorized through the umbilicus to perform conventional surgery. RESULTS: Mean operating time was 50.9 minutes (range, 30 to 120) for laparoscopies and 44 minutes (range, 15 to 80) for retroperitoneoscopy. There were 11 conversions (8 appendectomies, 3 varicocelectomies) and no postoperative complications. CONCLUSIONS: "One-trocar surgery" is safe, effective, and fast with a low complication rate and excellent cosmetic results. The authors believe it is the least invasive as well as the most effective approach in the treatment of varicocele, appendicitis, and selected intestinal diseases.

Adolescent↗

PubMed2001

Unusual clinical presentation of a rare case of phyllodes tumor of the breast in an adolescent girl.

Phyllodes tumor of the breast is a very rare neoplasm, particularly in adolescent girls and young women. It usually presents as unilateral palpable mass. The authors report the case of an adolescent girl who presented at the Emergency Department with bloody nipple discharge. Although the clinical signs suggested an intraductal tumor, the histologic examination showed a phyllodes tumor. The management and the biologic behavior of this uncommon tumor are discussed with particular regard to the very unusual clinical presentation in this patient. J Pediatr Surg 36:941-943.

Adolescent↗

PubMed2001

Macrophage response to Mycobacterium tuberculosis during HIV infection: relationships between macrophage activation and apoptosis.

Human macrophages represent the first line of defense for the containment of Mycobacterium tuberculosis infection. After phagocytosis, macrophages express activation surface markers and produce proinflammatory cytokines and chemokines whose main role is to control pathogen spreading by recruiting peripheral lymphocytes and monocytes at the site of inflammation. However, in the case of a concomitant human immunodeficiency virus (HIV) infection, these signals strongly enhance the susceptibility to viral infection both at the viral entry and replication levels. Under these conditions, viral expansion extends beyond tissue macrophages to T cells and vice-versa, according to the emerging viral phenotype. In absence of an efficient immune response, Mycobacterium tuberculosis can replicate in macrophages in an uncontrolled fashion culminating in macrophage death by apoptosis. As a consequence, a more severe form of immunedepression, involving both innate and specific immune responses, could be responsible for both ematogenous mycobacterial dissemination and extrapulmonary form of tuberculosis in HIV-infected patients.

Apoptosis↗