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At least 1,297 records · Page 72Linked to original sources
PubMed1985

Kinetics of tachyphylaxis to mediators of acute inflammation.

The kinetics of vascular leakage and tachyphylaxis induced by histamine and bradykinin were examined in rabbit skin and were compared with the kinetics of tachyphylaxis of neutrophil accumulation in lesions induced with the chemotaxin formylmethionyl-leucyl-phenylalanine (FMLP). Maximal leakage of 125I-human serum albumin occurred during the first 5 min after injection of bradykinin and from 10 to 20 min after injection of histamine. Tachyphylaxis developed within 30 min of injection of bradykinin and 1 hr after injection of histamine. For both agents, there was a linear regression of sensitivity with time from 8 hr to 4 days, with normal sensitivity estimated to return at 4.6 days for bradykinin and 4.7 days for histamine. Marked cross-desensitization occurred between the two agents, and lesions initiated with the chemotaxin FMLP were desensitized to restimulation with a mixture of histamine and bradykinin. Initiation of lesions with histamine and bradykinin did not diminish the accumulation of neutrophils when lesions were restimulated with FMLP. The kinetics of tachyphylaxis of neutrophil accumulation in lesions stimulated with FMLP exhibited a linear regression of sensitivity on time between 4 days and 10 days, with estimated resensitization at 11.9 days. Histamine and bradykinin induce enhanced vascular permeability when endothelial cells in post-capillary venules contract following stimulation of their membrane receptors for these agents. We have recently proposed that the migration of neutrophils into acute inflammatory lesions is regulated by a mechanism coupled to chemotaxin receptors which may be similarly located on endothelial cells within the lesions. The present experiments indicate that expression of receptors for vascular permeability agents and the chemotaxin FMLP are independent events with distinct kinetics.

Animals↗
PubMedDate not supplied

Cellular immunity in myasthenia gravis after thymectomy and corticosteroid therapy.

Clinical and immunological changes in patients with myasthenia gravis (MG) who had extended thymectomy (Tx) and/or corticosteroid therapy were examined to elucidate the mechanisms of improvement following the treatments. The changes found were: 1) After Tx and steroid therapy, in patients with MG who showed clinical improvement, the CD4/CD8 ratio and B lymphocyte subpopulations were markedly decreased. 2) Linear correlations between two T-cell subsets were evident in CD3 against CD4 and CD4/CD8 against CD4 after both Tx and steroid therapy. 3) T lymphocytes-CD8 decreased immediately after Tx and returned to pre-treatment levels within three weeks. 4) Cellular sensitization against a nicotine acetylcholine receptor (AChR)-like protein isolated from fetal calf thymus decreased after steroid therapy. These results indicate that clinical improvement in MG after the treatments was accompanied by a decrease in helper/inducer T lymphocytes, B lymphocytes and specific lymphocyte sensitization against nicotinic AChR.

Adolescent↗
PubMed1992

Regulation of macrophage colony-stimulating factor in liver fat-storing cells by peptide growth factors.

Macrophage colony-stimulating factor (M-CSF) selectively promotes mononuclear phagocyte survival, proliferation, and differentiation. The production of this factor within the liver may be necessary to support the relatively long-term survival of circulating monocytes as they migrate into tissues and differentiate into macrophages. We studied the constitutive expression and the effects of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) on M-CSF mRNA levels and secretion of M-CSF in murine liver fat-storing cells (FSC), vascular pericytes likely involved in the development of liver fibrosis. By Northern analysis, using a murine M-CSF cDNA, FSC constitutively express two major transcripts of 4.4 and 2.2 kb, similar to those detected in mouse L cells, used as a control. Exposure to 10 ng/ml PDGF or bFGF increased M-CSF mRNA levels. Peak effects were observed at 3 and 6 h for PDGF and bFGF, respectively, returning to baseline levels by 12 h. Under basal conditions, detectable amounts of M-CSF, measured by radioimmunoassay, were found in cell supernatants conditioned for 8 and 24 h. PDGF and bFGF markedly stimulated the release of M-CSF as early as 8 h, an effect persisting for at least 24 h. These findings suggest that liver FSC release M-CSF upon stimulation by PDGF and bFGF and may contribute to the activation of resident or infiltrating cells in inflammatory liver diseases.

Animals↗
PubMed1990

Gallstone pancreatitis.

Gallstone pancreatitis is caused by transient obstruction of the ampulla of Vater by a migrating gallstone. Intraglandular activation of pancreatic enzymes occurs (by an unclear mechanism), and their entry into the circulation causes most of the local and systemic events of pancreatitis. The diagnosis is based on history and physical examination, an elevation of serum amylase above 1000 IU/L, and ultrasound and CT scans. Endoscopic retrograde cholangiopancreatography can be used in less certain cases to confirm the presence of common bile duct stones. Because of the absence of an agent that can abort progression of the disease, therapy should consist of adequate resuscitation, nutritional support, and careful monitoring to detect early complications. In patients with mild pancreatitis, surgery usually can be performed within 48 or 72 hours of admission or as soon as symptoms and amylase levels return to normal. For patients with severe disease, endoscopic sphincterotomy is emerging as the therapeutic modality of choice. Elective treatment of the associated biliary disease should be performed during the same hospitalization after the acute phase of the disease has subsided.

Acute Disease↗
PubMed2000

Release of neuropeptide Y and hemodynamic changes during surgical removal of human pheochromocytomas.

This study investigates the release of Neuropeptide Y from eight human pheochromocytomas. Profil immunoreactive Neuropeptide Y (Ir-NPY) levels during the management of surgery were compared with these of norepinephrine (NE) while hemodynamics were monitored. Plasma IrNPY and NE levels increased during tumor manipulation and returned to near normal one hour after operation. However, Ir-NPY levels remained high just after tumor resection while NE levels were significantly decreased. At tumor manipulation and just after tumor resection, plasma Ir-NPY levels were correlated with the systemic vascular resistances (SVR) (r = 0.74; P<0.04 and r = 0.86; P<0.006 respectively). No correlation was found either between plasma Ir-NPY and NE levels or between plasma NE levels and SVR. The release of Ir-NPY from tumor tissue, studied by a superfusion method, exhibited a significant correlation with the plasma Ir-NPY concentrations at the time of corresponding tumor resection (r = 0.95; P<0.007). Chromatographic analysis showed that Ir-NPY in plasma and outflow migrate as human NPY (1-36). These results confirmed that in pheochromocytoma, plasma NPY mainly originates from the tumor and argue for an important role of NPY in pheochromocytoma hypertension as indicated by the correlation between the Ir-NPY levels and the SVR.

Adrenal Gland Neoplasms↗
PubMed2000

Dendritic cell-based cancer immunotherapy: potential for treatment of colorectal cancer?

Human tumours including those of the gastrointestinal tract express a number of specific antigens that can be recognized by T cells, thus providing potential targets for cancer immunotherapy. Dendritic cells (DC) are rare leucocytes that are uniquely potent in their ability to capture, process and present antigens to T cells, and so selectively migrate through tissues to reach lymph nodes and spleen where initiation of immune responses takes place. Studies in murine tumour models have shown clearly that DC are capable of presenting tumour antigens to initiate tumour-specific cytotoxic T cell responses, and DC vaccination can induce anti-tumour activity against both primary tumours and pre-established tumour metastases. These findings together with the ability to culture sufficient numbers of DC from human bone marrow or blood progenitors have prompted the current major interest in their potential use in human tumour vaccination. Vaccine production involves harvesting autologous DC from cultured peripheral blood mononuclear cells in the presence of a cocktail of cytokines, ex vivo exposure of the DC to tumour antigens and return of pulsed DC to the patient to induce tumour immunity. Reports from Phase I/II clinical trials indicate that DC vaccines are safe with little or no side effect, and are capable of initiating antigen-specific T cell responses. Furthermore, defined tumour antigens are not necessarily required, which may make the process more applicable to human cancers, including many gastrointestinal cancers that lack well-characterized tumour-specific antigens. Additional trials of DC vaccination for a variety of human cancers including colorectal cancers are under way, and refinement of vaccine protocols and methods for targeting tumour antigens to DC in vivo are also being explored. There is reason to believe that DC-based vaccination could become an adjunct to current treatments for human cancers including colorectal cancer in the foreseeable future.

Clinical Trials as Topic↗
PubMed1998

Mechanisms of acid-base regulation in migrant sea lampreys (Petromyzon marinus) following exhaustive exercise

The life cycle of the sea lamprey (Petromyzon marinus) is characterized by a terminal upstream spawning migration that may be associated with brief bursts of high-intensity swimming. Such activity usually leads to pronounced blood acid-base disturbances in fishes, but lampreys rapidly correct these perturbations within 1 h. In the present study, patterns of post-exercise H+ excretion (JHnet) and ion movements were followed in sea lampreys to test the hypothesis that dynamic manipulation of Na+ versus Cl- movements across the animal's body surface, presumably at the gills, accounted for the rapid restoration of blood pH following exercise. The first hour of post-exercise recovery in sea lampreys was associated with marked stimulation of JHnet (equivalent to base uptake), which approached -500 micromol kg-1 h-1. After 1 h, JHnet patterns had returned to resting rates. Analyses of net Na+ and Cl- movements (JNanet, JClnet) suggested that elevated net Cl- losses, which greatly exceeded net Na+ losses, accounted for most of the JHnet. Subsequent experiments, using radiotracers (22Na+, 36Cl-), indicated that differential increases in Cl- versus Na+ permeability accounted for the greater post-exercise Cl- losses and the corresponding stimulation of net proton excretion. Finally, metabolic acid budget analyses confirmed our hypothesis that rapid excretion of metabolic protons was the primary means used by sea lampreys to correct post-exercise extracellular acidosis.

Journal Article↗
PubMed1986

Occupational and spatial mobility of temporary Mexican migrants to the U.S.: a comparative analysis.

"U.S. job and spatial mobility are compared here for recent returnee migrants from two Mexican areas--Rio Grande, Zacatecas, in the interior; and Nueva Rosita-Muzquiz, Coahuila, near the U.S. border. Results suggest that the interior migrants fit a hierarchical migrant model: they move up the urban hierarchy from U.S. rural areas to towns and cities, experiencing substantial job mobility at first, but little after reaching the urban sector. Border migrants fit a shuttle migrant model: they return to the same job and place year after year, experiencing little or no spatial and occupational mobility, although they tend to hold somewhat higher status jobs."

Americas↗
PubMed1975

Cytological differentiation in the uropygial gland.

Ultrastructural changes were studied in the cells undergoing secretory differentiation in zone I of the tubules of the uropygial gland of White Plymouth Rock chickens. A layer of basal cells and four secretory stages are recognized as the cells migrate from the periphery to the lumen of tubules and progressively elaborate a secretion product. Basal cells, containing rough endoplasmic reticulum and free ribosomes, rest on the basement membrane and are the source from which secretory cells arise. Dilated perinuclear cisternae and the proliferation of smooth endoplasmic reticulum in the form of vesicles, invaginated sacs and cusp-shaped cisternae indicate the onset of lipgenesis in stage I cells. The perinuclear cisternae are more dilated and the endoplasmic reticulum is composed on saccules and cisternae in stage II cells. Stage III cells are characterized by concentric lamellae of endoplasmic reticulum surrounding secretory droplets. Dilated cisternae of endoplasmic reticulum and secretory droplets both contain a reticular substance. The perinuclear cisternae of stage III cells have returned to normal dimensions. Large mature lucent secretory droplets, lined with electron-dense material, fill the cytoplasm ostage IV cells which degenerate and release their secretory product into the tubule lumen. Spherical membrane-bound compartments containing a mottled substance of moderate electron density occur in basal cells and all subsequent secretory stages. These mottled bodies are surrounded by saccules of endoplasmic reticulum in stage II cells and are intimately associated with secretory droplets in stage III cells, but there is no evidence that they give rise to secretory droplets and their role in secretory differentiation is unknown.

Animals↗
PubMed1992

Subureteral collagen injection for the endoscopic treatment of vesicoureteral reflux in children. Followup study of 97 treated ureters and histological analysis of collagen implants.

Endoscopic subureteral injection has become an established alternative means for treating vesicoureteral reflux in select children. However, which injection material to use remains a controversy. Polytetrafluoroethylene (Teflon) has been injected in more than a thousand patients with few complications, although experimental and clinical studies have demonstrated migration of the injected particles into distant organs, such as the lungs and the brain, as well as local and metastatic granuloma formation. Therefore, we introduced, following experimental studies in the mini-pig model, glutaraldehyde cross-linked, highly purified bovine collagen for injection. Between June 1988 and October 1991, 97 refluxing ureters in 66 children were treated by endoscopic subureteral collagen injection. In 58.8% of the ureters reflux was cured after 1 and in 77.3% after 2 injections. Considering improvement to grades I and II reflux without further treatment as success, the success rate increased to 68.0% after 1 and to 89.7% after 2 injections. Mean followup was 18.5 months (range 3 to 39 months). After 2 failed injections the patients either returned to antibiotic long-term prophylaxis or the reflux was operatively corrected. The operative procedure was never compromised by the preceding injection. A direct correlation between deficient length of the submucosal tunnel of the intravesical ureter and the iatrogenic malposition of the collagen deposits, and the failures could be demonstrated. Granuloma formation at the site of injection was not found. The results of the histological investigation of the collagen deposits removed at open ureteral reimplantation for failures are reported. It could be demonstrated that endogenous fibroblasts invade the bovine collagen implant and that these cells show active production of new human collagen, types I and III, replacing the implant.

Adolescent↗
PubMed1982

Immunology of human gastric cancer: a preliminary report.

The immunological spectrum in fifteen patients with gastric cancer is presented. Patients were divided in three groups. Those with nonadvanced cancer, those with advanced but resectable lesions and those with advanced but nonresectable tumors. Preoperatively, elevated levels of circulating immune complexes (CIC) associated with hyporesponsiveness to phytohemagglutinin (PHA) and in mixed lymphocyte culture (MLC) as well as a positive leukocyte inhibitory serum factor (LIF-S) were found in nearly half of the patients. Inhibitory or enhancing autologous serum factors were detected. Postoperatively, immunologic parameters return to normal in patients with nonadvanced cancer, while in advanced cancer, antibody and cell-mediated immune response remained altered, with some changes associated with chemotherapy. These findings are probably related with the presence or absence of tumor and offer a distinct approach in evaluating the immunologic response of a tumor-bearing patient.

Adult↗
PubMed2005

The effects of carbohydrate supplementation during the second of two prolonged cycling bouts on immunoendocrine responses.

The purpose of this study was to examine the effect of carbohydrate (CHO) feeding during the second of two 90-min cycling bouts (EX1 started at 09:00 and EX2 started at 13:30) at 60% VO2max on leucocyte redistribution, neutrophil degranulation and oxidative burst and plasma IL-6 and stress hormone responses. This study consisted of two trials, which were completed in a counterbalanced order and separated by at least 4 days. Subjects (n=9) consumed a lemon flavoured 10% w/v CHO (glucose) or placebo (PLA) beverage during EX2: 500 ml just before exercise and 250 ml every 20 min during exercise. Venous blood samples were taken 5 min before exercise, immediately post-exercise, and 18-h post-EX2 for both trials. The main findings of this study were that ingestion of CHO compared with PLA during EX2 better maintained plasma glucose concentration, blunted the responses of plasma adrenaline, ACTH, cortisol, GH and IL-6, and attenuated the leukocytosis and monocytosis, but had no effect on neutrophil degranulation and oxidative burst activity. Furthermore, the immunoendocrine disturbances induced by two bouts of prolonged exercise returned to resting values within 18 h. These findings suggest that ingestion of CHO compared with PLA during the second of two bouts of 90-min cycling at 60% VO2max better maintains plasma glucose, blunts hypothalamic-pituitary-adrenal activation, and attenuates leucocyte trafficking, but does not affect neutrophil function. Furthermore, the disturbances of immunoendocrine responses induced by two bouts of prolonged exercise on the same day recover within 18 h.

Adrenocorticotropic Hormone↗
PubMed1986

Internalization and recycling of transferrin and its receptor. Effect of trifluoperazine on recycling in human erythroleukemic cells.

When human erythroleukemic (K562) cells were incubated with 25 microM trifluoperazine (TFP), a drug that inhibits both calmodulin-dependent and calcium-activated phospholipid-dependent kinases, the number of transferrin receptors detected on the cell surface was reduced to approximately half with no change in the affinity of the remaining surface receptors. Removal of the TFP from the incubation medium reversed the loss of surface receptors and they returned to the cell surface in an apparently synchronous manner. As a result, the number of receptors detected on the cell surface exceeded the original level but later returned to normal. Measurements of the total number of receptors available to transferrin in TFP-treated cells suggested that the lost receptors were not participating in the internalization and recycling pathway but instead were probably trapped at an intracellular location. However, those receptors that remained on the cell surface continued to internalize transferrin and to recycle apotransferrin to the cell surface albeit more slowly than in cells that had not been treated with TFP. Using transferrin that had been labeled with iron-59, it was found that although iron uptake was reduced in line with the diminished number of surface receptors, iron still accumulated within TFP-treated cells, suggesting that in the presence of the drug, transferrin-transferrin receptor complexes continued to migrate through an intracellular compartment that contained a low pH.

Cells, Cultured↗
PubMed1991

Effect of cigarette smoking on the levels of platelet-activating factor-like lipid(s) in plasma lipoproteins.

The effect of cigarette smoking on the levels of platelet-activating factor-like lipid(s) (PAF-LL) in plasma lipoproteins was studied. The subjects were 10 healthy male non-smokers (24 +/- 1.4 years old) and 13 healthy male habitual smokers (23 +/- 1.3 years old). Fasting venous blood was obtained and basal levels of PAF-LL in plasma lipoproteins were estimated. The acute effect of cigarette smoking was also studied in smokers. Plasma lipoproteins were separated by ultracentrifugation. Lipids were extracted and separated by thin-layer chromatography. The fraction with the same migration as authentic PAF was recovered and was shown to cause aggregation of human polymorphonuclear neutrophils. This activity was identified as PAF-LL because it was inactivated by phospholipase A2 and was blocked by CV-3988, an antagonist of the PAF receptor. PAF-LL was detected in LDL and HDL, but not in VLDL or in lipoprotein-deficient plasma. The levels of PAF-LL in LDL in non-smokers, and in smokers before and after smoking were 13 +/- 7.5, 16 +/- 14.9 and 190 +/- 179.0 pg/ml, and those in HDL were 12 +/- 5.2, 40 +/- 40.0 and 235 +/- 205.1 pg/ml, respectively. The values in both LDL and HDL in smokers increased significantly after smoking (P less than 0.05). After 30 min, the levels had returned almost to the pre-smoking levels. We conclude that cigarette smoking induces an increase in the levels of PAF or closely related lipid(s) in LDL and HDL, which may be related to smoking-induced atherosclerosis.

Adult↗
PubMed2005

Abnormal heart rate turbulence predicts the initiation of ventricular arrhythmias.

BACKGROUND: Abnormal heart rate turbulence (HRT) reflects autonomic derangements predicting all-cause mortality, yet has not been shown to predict ventricular arrhythmias in at-risk patients. We hypothesized that HRT at programmed ventricular stimulation (PVS) would predict arrhythmia initiation in patients with left ventricular dysfunction. METHODS: We studied 27 patients with coronary disease, left ventricular ejection fraction (LVEF) 26.7 +/- 9.1%, and plasma B-type natriuretic peptide (BNP) 461 +/- 561 pg/mL. Prior to arrhythmia induction at PVS, we measured sinus cycles after spontaneous or paced premature ventricular contractions (PVCs) for turbulence onset (TO; % cycle length change following PVC) and slope (TS; greatest slope of return to baseline cycle). T-wave alternans (TWA) was also measured during atrial pacing. RESULTS: At PVS, abnormal TO (> or =0%) predicted inducible ventricular tachycardia (VT; n = 10 patients; P < 0.05). TO was greater in inducible than in noninducible patients (2.3 +/- 3.1% vs -0.02 +/- 2.8%, P < 0.05) and correlated with LVEF (P < 0.05) but not with BNP. TS did not differ between groups. Conversely, ambulatory HRT differed significantly from HRT at PVS (TO -0.55 +/- 1.08% vs 0.85 +/- 3.02%, P < 0.05; TS 2.63 +/- 2.09 ms/RR vs 8.70 +/- 6.56 ms/RR, P < 0.01), and did not predict inducible VT but trended (P = 0.05) to predict sustained VT on 739 +/- 179 days follow-up. TWA predicted inducible (P < 0.05) and spontaneous (P = 0.0001) VT but did not co-migrate with HRT. CONCLUSIONS: Abnormal HRT measured at PVS predicted the induction of sustained ventricular arrhythmias in patients with ischemic cardiomyopathy. However, HRT at PVS did not correlate with ambulatory HRT, nor with TWA, both of which predicted spontaneous ventricular arrhythmias. Thus, HRT may reflect the influence of autonomic milieu on arrhythmic susceptibility and is likely complementary to traditional arrhythmic indices.

Aged↗
PubMed2002

[Results of excision of the radial head in comminuted fractures].

OBJECTIVES: To evaluate the results of radial head excision in the treatment of comminuted radial head fractures. METHODS: The study included 20 patients (14 men, 6 women; mean age 34 years; range 21 to 55 years) who underwent radial head excision for comminuted, closed fractures. Sixteen patients had Mason type 3 and four patients had type 4 fractures. Surgery was performed at a mean of eight days after trauma (range 1 to 30 days). Patients were assessed with regard to whether they were able to return their former activities and work, and whether they had pain, limitation, loss of strength, and instability. The results were evaluated by the Radin and Riseborough's classification. The mean follow-up period was seven years (range 2 to 12 years). RESULTS: Sixteen patients (80%) re-gained their previous activities or work. Nine patients became asymptomatic. Five patients complained of loss of strength in the arm. Pain associated with weight bearing was observed in two patients in the wrist and elbow, respectively, and in both in two patients. Two patients had limitation of more than 30 degrees in at least one of extension, flexion, supination, or pronation. Five patients had mediolateral instability. The mean elbow flexion was 125 degrees (range 100 to 140 degrees). Proximal migration of the radius was detected in five patients (1 mm), two patients (3 mm), and in three patients (5 mm). According to the Radin and Riseboroughs classification, nine (45%), seven (35%), and four (20%) patients had good, fair, and poor results, respectively. CONCLUSION: Despite its relevance in elbow kinematics, our results seem to justify excision of the radial head in Mason type 3 comminuted radial head fractures where internal fixation presents severe difficulties.

Adult↗
PubMed2000

Manometric evidence of improved early gastric stasis by erythromycin after pylorus-preserving pancreatoduodenectomy.

Gastric stasis is a frequent complication of pylorus-preserving pancreatoduodenectomy (PPPD). We demonstrated that it might be attributable to delayed recovery of phase III activity of the gastric migrating motor complex due to low concentrations of plasma motilin caused by resection of the duodenum. Leucine 13-motilin is effective for treating gastric stasis, but it is not yet available for clinical use. Whether erythromycin would improve early gastric stasis after PPPD was tested clinically and by manometry. A manometric tube assembly and a gastrostomy tube were inserted in the stomach of 10 patients at PPPD for pressure recording from the gastric antrum and jejunum and for gastric juice drainage, respectively. After baseline recording, erythromycin 5 mg/kg was given intravenously on day 14 and saline as a placebo on day 17 every 4 hours four times a day. The daily volume of gastric juice output and the gastric motility index were measured. The mean period until the return of gastric phase III was 31 +/- 1 days. Erythromycin significantly increased the gastric motility index from 7.9 +/- 1.3 mmHg to 15.7 +/- 1.8 mmHg (p = 0.0005), whereas saline did not (7.2 +/- 1.6 mmHg to 6.5 +/- 1.2 mmHg; p = 0.21). Erythromycin significantly decreased the gastric juice output from 1,080 +/- 190 ml to 738 +/- 199 ml (p < 0.0001), but the saline injections did not (1,064 +/- 174 ml to 1,115 +/- 189 ml; p = 0.35). Erythromycin, a universally available motilin agonist, is a safe, effective, potent drug for the treatment of early gastric stasis after PPPD.

Aged↗
PubMed2000

Bacterial clearance and survival are dependent on CXC chemokine receptor-2 ligands in a murine model of pulmonary Nocardia asteroides infection.

Survival from murine pulmonary nocardiosis is highly dependent on CXC chemokine receptor-2 (CXCR2) ligand-mediated neutrophil chemotaxis and subsequent clearance of the infectious agent Nocardia asteroides. Intratracheal inoculation of N. asteroides rapidly up-regulated the CXC chemokines macrophage inflammatory protein-2 (MIP-2) and KC within 24 h, with levels remaining elevated through day 3 before returning to near baseline levels by day 7. Coinciding with elevated MIP-2 and KC were the rapid recruitment of neutrophils and clearance of the organism. Anti-Ly-6G Ab-mediated neutrophil depletion before bacterial challenge resulted in strikingly increased mortality to N. asteroides infection. The relative contribution of MIP-2 in neutrophil recruitment was examined by anti-MIP-2 Ab treatment before nocardial infection. MIP-2 neutralization had no detrimental effects on survival, neutrophil recruitment, or bacterial clearance, suggesting the usage of additional or alternative CXCR2-binding ligands. The importance of the CXC family of chemokines was determined by the administration of an anti-CXCR2 Ab capable of blocking ligand binding in vivo. Anti-CXCR2 treatment greatly increased mortality by preventing neutrophil migration into the lung. Paralleling this impaired neutrophil recruitment was a 100-fold increase in lung bacterial burden. Combined, these observations indicate a critical role for neutrophils and CXC chemokines during nocardial pneumonia. These data directly link CXCR2 ligands and neutrophil recruitment and lend further support to the concept of CXC chemokine redundancy. For infections highly dependent on neutrophils, such as nocardial pneumonia, this is of critical importance.

Amino Acid Sequence↗