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PubMed2000

Significantly high regional morbidity of MPO-ANCA-related angitis and/or nephritis with respiratory tract involvement after the 1995 great earthquake in Kobe (Japan).

Within a 3-year period after the Great Earthquake of Kobe (Japan) resulted in more than 6,000 deaths and complete destruction of the central area of Kobe City, 14 patients (group 1 [G1]) with myeloperoxidase (MPO)-antineutrophil cytoplasmic autoantibody (ANCA)-related angitis and/or nephritis presented to Nishi-Kobe Medical Center in western Kobe City. On the other hand, only 15 patients with this disease were encountered between 1990 and 1997 at Kyoto University Hospital in Kyoto City, which is located 80 km from Kobe City and was only minimally affected by the earthquake. These 15 patients and 1 patient who presented to Nishi-Kobe Medical Center before the Great Earthquake were classified as group 2 (G2). Although the average MPO-ANCA titer in G1 was almost the same as that in G2, G1 showed a significantly greater average value for white blood cells than G2 (11,321 +/- 4,369 versus 8,116 +/- 2, 389/microL; P < 0.05). Concerning renal function, a significant elevation in creatinine (Cr) levels at diagnosis (7.4 +/- 3.8 versus 2.1 +/- 1.4 mg/dL; P < 0.01) and rapidly declining rates of reciprocal Cr levels were noted in G1 (0.325 +/- 0.304 versus 0.087 +/- 0.069 dL/mg. wk; P < 0.01). The number of patients who required emergency hemodialysis was significantly greater in G1 than G2 (nine versus three patients; P < 0.02); however, the incidence of renal death and mortality were not significantly different between the groups. The number of patients who reported upper respiratory tract inflammation as an initial symptom was also significantly greater in G1 than G2 (eight versus two patients; P < 0.01). Moreover, patients in G1 experienced a significantly greater rate of severe pulmonary involvement during the hospital course than G2 (pulmonary hemorrhage, five versus no patients; interstitial pneumonitis, four versus two patients, respectively; P < 0.01). The relatively uniform and distinctive clinical features of the disease after the Great Earthquake, in conjunction with a high morbidity, suggest a relationship between disease development and this urban type of earthquake. Severely provoking air pollution caused by massive destruction and reconstruction of the city may have caused high frequencies of upper respiratory tract inflammation as an initial symptom and severe pulmonary involvement.

Aged↗
PubMed2002

Extrabranchial chemoreceptors involved in respiratory reflexes in the neotropical fish Colossoma macropomum (the tambaqui).

In a previous study, complete denervation of the gills in the tambaqui Colossoma macropomum did not eliminate the increase in breathing amplitude seen during exposure of this species to hypoxia. The present study was designed to examine other sites of putative O(2)-sensitive receptors that could be involved in this reflex action. Superfusion of the exposed brain of decerebrate, spinalectomized fish did not reveal the presence of central chemoreceptors responsive to hyperoxic, hypoxic, hypercarbic, acidic or alkaline solutions. Subsequent central transection of cranial nerve IX and X, removing not only all innervation of the gills but also sensory input from the lateral-line, cardiac and visceral branches of the vagus nerve, did not eliminate the increase in breathing amplitude that remained following peripheral gill denervation alone. Administration of exogenous catecholamines (10 and 100 nmol kg(-1) adrenaline) to fish with intact brains and minimal surgical preparation reduced both respiratory frequency and amplitude, suggesting that humoral release of adrenaline also could not be responsible for the increase in breathing amplitude that remained following gill denervation. Denervation of the mandibular branches of cranial nerve V and the opercular and palatine branches of cranial nerve VII in gill-denervated fish (either peripheral gill denervation or central section of cranial nerves IX and X), however, did eliminate the response. Thus, our data suggest that hypoxic and hyperoxic ventilatory responses as well as ventilatory responses to internal and external injections of NaCN in the tambaqui arise from O(2)-sensitive receptors in the orobranchial cavity innervated by cranial nerves V and VII and O(2)-sensitive receptors on the gills innervated by cranial nerves IX and X. Our results also revealed the presence of receptors in the gills that account for all of the increase in ventilation amplitude and part of the increase in ventilation frequency during hyperoxic hypercarbia, a group or groups of receptors, which may be external to the orobranchial cavity (but not in the central nervous system), that contribute to the increase in ventilation frequency seen in response to hyperoxic hypercarbia and the possible presence of CO(2)-sensitive receptors that inhibit ventilation frequency, possibly in the olfactory epithelium.

Animals↗
PubMed1990

Involvement of respiratory muscles in cytoplasmic body myopathy--a pathology study.

A muscle biopsy and autopsy study of a child who died at 14 months of respiratory failure is described. A diagnosis of infantile cytoplasmic body myopathy was made due to the high percentage of cytoplasmic bodies (CBs), particularly in respiratory muscles. No pathological abnormalities were found in the central nervous system, peripheral nerves or visceral organs. Immunohistochemical studies suggested that the central core of CBs was stained for fibrillary actin, being surrounded by a positive signal for desmin. A differential diagnosis as to other conditions involving proliferation of CBs is discussed.

Autopsy↗
PubMed1990

Damage of Escherichia coli cells by t-butylhydroperoxide involves the respiratory chain but is independent of the presence of oxygen.

The action of t-butylhydroperoxide (tBOOH) on Escherichia coli cells has been studied as a model system for organic peroxide toxicity. Exposure of E. coli cells to tBOOH led to progressive and irreversible impairment of the respiratory function, an effect which was dependent on the availability of substrate. The effect of tBOOH on growth of E. coli with different carbon sources and alternative terminal electron acceptors was investigated. It was found that the sensitivity of E. coli to tBOOH under diverse growth conditions implicating a functional respiratory chain was greater than when the bacterium grew by fermentation. Also the mutant E. coli SASX76, which requires exogenous 5-aminolevulinic acid to synthesize the cytochromes, was more resistant to tBOOH when lacking a functional respiratory chain. These data point to the respiratory chain as a major target in the in vivo action of tBOOH. Experiments with isolated membranes also showed a tBOOH-induced damage of the respiratory chain monitored by impairment of the NADH oxidase. The effect of tBOOH was produced even under anaerobiosis, indicating that development of cell damage was independent of oxygen and, therefore, that neither oxygen-derived radicals nor lipid peroxidation were involved.

Cell Membrane↗
PubMed1997

Lumenal proteins involved in respiratory electron transport in the cyanobacterium Synechocystis sp. PCC6803.

Cyanobacterial thylakoids catalyze both photosynthetic and respiratory activities. In a photosystem I-less Synechocystis sp. PCC 6803 strain, electrons generated by photosystem II appear to be utilized by cytochrome oxidase. To identify the lumenal electron carriers (plastocyanin and/or cytochromes c553, c550, and possibly cM) that are involved in transfer of photosystem II-generated electrons to the terminal oxidase, deletion constructs for genes coding for these components were introduced into a photosystem I-less Synechocystis sp. PCC 6803 strain, and electron flow out of photosystem II was monitored in resulting strains through chlorophyll fluorescence yields. Loss of cytochrome c553 or plastocyanin, but not of cytochrome c550, decreased the rate of electron flow out of photosystem II. Surprisingly, cytochrome cM could not be deleted in a photosystem I-less background strain, and also a double-deletion mutant lacking both plastocyanin and cytochrome c553 could not be obtained. Cytochrome cM has some homology with the cytochrome c-binding regions of the cytochrome Caa3-type cytochrome oxidase from Bacillus spp. and Thermus thermophilus. We suggest that cytochrome cM is a component of cytochrome oxidase in cyanobacteria that serves as redox intermediate between soluble electron carriers and the cytochrome aa3 complex, and that either plastocyanin or cytochrome c553 can shuttle electrons from the cytochrome b6f complex to cytochrome cM.

Amino Acid Sequence↗
PubMed2002

Clinical spectrum of inflammatory myositis in South India--a ten year study.

OBJECTIVE: To describe the clinical spectrum of inflammatory myopathies at a referral hospital in South India. METHODS: Patients were assessed for the pattern of muscle involvement, for the presence of arthritis, Raynaud's phenomenon, interstitial lung disease (ILD) and cardiac involvement. Muscle enzymes, electromyogram (EMG) and muscle biopsies were done. RESULTS: Eighty seven patients with inflammatory myopathies were encountered over 10 years. These included 24 with adult polymyositis, 26 with adult dermatomyositis, one with amyopathic dermatomyositis, five with juvenile myositis, one with dermatomysitis following carcinoma breast and 30 with overlap with other connective tissue diseases. There was a female preponderance (M:F = 1:2.35) except in juvenile myosits group (M:F = 1.5:1). The mean age of onset in years was 33.26 in adult polymyositis, 35.03 in adult dermatomyositis, 7.4 in juvenile dermatomyositis, 42 in malignancy-associated dermatomyositis and 25.51 in the overlap group. Proximal muscle weakness was seen in 98.8% patients, dysphagia in 33.3%, distal muscle weakness in 12.5%, respiratory muscle weakness in 9.2% and dysphonia in 4.6%. Other features included arthritis 35.63%, interstitial lung disease (ILD) 9.2%, Raynaud's 5.7%, myocarditis 4.6% and conduction disturbances 1.15%. Eleveated muscle enzymes were seen in 85.1% patients. Eletromyogram was positive in 66.6%. Muscle biopsy was positive in 85.29%. Anti-nuclear antibody was positive in 67.24%. All received steroids, non-responders needed methotrexate (13 patients) or azathioprine (11 patients). Death occurred in 10 (seven with dermatomyositis predominantly due to respiratory involvement and three with overlap). CONCLUSION: There was female preponderance except in juvenile myositis group. Proximal muscle weakness was the commonest feature. ILD was the commonest respiratory problem, while myocarditis was the commonest cardiac problem seen. Response to therapy and prognosis in polymyositis were good with no mortality during the study period. Death in the dermatomyositis group was mainly due to respiratory involvement.

Adolescent↗
PubMed2006

[Neuromuscular disorders - assessment of the respiratory muscles].

Involvement of respiratory muscles is a nearly constant feature of neuromuscular disorders, leading to respiratory failure. A careful respiratory follow up adapted to the variable time course of each disease is therefore mandatory. As the first step, a systematic clinical evaluation is essential to detect the subtle respiratory symptoms and signs related to respiratory muscle failure. Dyspnea and orthopnea are often late findings in patients with a usually severe functional impairment due to peripheral muscle weakness. Nocturnal respiratory events (obstructive sleep apnea syndrome and hypoventilation) are strongly suggested by daytime hypersomnolence and frequent morning headaches. Physical evaluation is essential to detect accessory muscle recruitment, supine abdominal paradox, and encumbrance of upper or lower airways. Vital capacity (VC) is the most classical lung function test. The major limitation of spirometry is its poor sensitivity to detect a moderate inspiratory muscle weakness. Supine VC may improve the detection of diaphragmatic involvement. Peak expiratory flow during cough (cough PEF) gives an overall evaluation of cough efficiency, values below 160 to 270 L/min suggesting poor airway clearance. Arterial blood gases are performed in case of clinical signs, significant deterioration of lung function tests, or sleep desaturations. Hypercapnia is weakly related to lung function results in patients with Steinert dystrophy and those with bulbar involvement. A specific evaluation of respiratory muscle strength is mandatory, as these tests are both sensitive and highly prognostic. Possible discrepancies (particularly in bulbar patients) between maximal inspiratory pressure (PImax) and sniff nasal inspiratory pressure (SNIP) justify to perform both measurements and to select the highest pressure. A maximal expiratory pressure (PEmax) below 45 cm H2O may indicate a compromised cough efficiency but the correlation with cough PEF may be poor. A screening nocturnal oxymetry is useful to detect sleep apneas and hypoventilation. Criteria defining significant desaturations remain however controversial. Suspicion of obstructive sleep apnea syndrome on clinical grounds or oxymetry findings should be confirmed by a conventional polysomnography.

Cough↗
PubMed2001

Meige syndrome secondary to basal ganglia injury: a potential cause of acute respiratory distress.

BACKGROUND: Meige syndrome is a movement disorder that includes blepharospasm and oromandibular dystonias. Its etiology may be idiopathic (primary) or it may arise secondary to focal brain injury. Acute respiratory distress as a feature of such dystonias occurs infrequently. A review of the literature on Meige syndrome and the relationship between dystonias and respiratory compromise is presented. METHODS: A 60-year-old woman suffered a cerebral anoxic event secondary to manual strangulation. She developed progressive blepharospasm combined with oromandibular and cervical dystonias. Neuroimaging demonstrated bilateral damage localized to the globus pallidus. Years later, she presented to the emergency department in intermittent respiratory distress associated with facial and cervical muscle spasms. RESULTS: Increasing frequency and severity of the disorder was noted over years. The acute onset of respiratory involvement required intubation and eventual tracheotomy. A partial therapeutic benefit of tetrabenazine was demonstrated. CONCLUSION: This case highlights two interesting aspects of Meige's syndrome: (1) Focal bilateral basal ganglia lesions appear to be responsible for this patient's movement disorder which is consistent with relative overactivity of the direct pathway from striatum to globus pallidus internal and substantia nigra pars reticularis; (2) Respiratory involvement in a primarily craniofacial dystonia to the point of acute airway compromise.

Airway Obstruction↗
PubMedDate not supplied

Legionnaires' disease pneumonia: histopathologic features and comparison with microbial and chemical pneumonias.

The histopathologic findings in lung tissue are reported from five cases of Philadelphia Legionnaire's Disease and the results are compared to pneumonias caused by other microbial and chemical agents. Histopathology of lung tissue was similar in all cases, despite the fact that death occurred between the fourth and 14th day of clinical illness. The inflammatory response was almost totally limited to the lower respiratory tract and primarily involved respiratory bronchioles, alveolar ducts and alveoli. Major bronchial branches and pulmonary interstices showed little or no involvement. There was considerable variation in the extent and nature of the consolidation, but the overall reaction pattern was highly characteristic of diffuse alveolar damage. Most involved areas showed intra-alveolar, fibrinocellular mononuclear cell predominant exudates, associated with pneumonocytic hyperplasia and slough. These findings plus the presence of erythroleucophagocytosis by macrophages and paucity of polymorphonuclear leucocytes are commonly associated with psittacine pneumonia, and much less so with classic patterns of bacterial, viral, fungal or rickettsial pneumonias. Of the toxic inhalants, nickel carbonyl, phosgene, nitrous oxide, cadmium oxide and some halogenated hydrocarbons have been associated with this tissue reaction pattern. Bacteria were notably absent in lung tissue stained by methods used to demonstrate the Legionnaires' Disease agent.

Adult↗
PubMed1988

Upper respiratory tract involvement in adult T-cell leukemia.

Adult T-cell leukemia (ATL) is characterized by peripheral lymph node enlargement, hepatosplenomegaly and skin lesions. The association of local mass lesions of other organs with ATL is extremely rare. This report describes a 57-year-old woman with chronic type ATL with associated local tumor masses in the nasal cavity, paranasal sinuses and larynx as well as skin infiltration. Histologic investigation of the skin lesion and nasal mucosa revealed non-Hodgkin lymphoma, diffuse, mixed type. Her chief complaints were progressive dyspnea and hoarseness. Leukemic cell masses in her upper respiratory tract caused narrowing of the airway, which was responsible for her complaints.

Deltaretrovirus Infections↗
PubMedDate not supplied

[Guillain-Barre syndrome. Experience in a third level hospital].

INTRODUCTION: Acute peripheral neuropathy represents a medical emergency. The causes of it are diverse and plentiful. The most common cause of acute paralytic peripheral neuropathy is the Guillain-Barré syndrome (GBS). As many as 85% of those affected can be expected to make an excellent recovery. OBJECTIVE: To describe the principal risk factors associated, clinical manifestations, treatment, evolution and complications of 28 cases of Guillain-Barré syndrome (GBS) in the "Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán". METHODS: We search in our computer records all files under diagnostic of GBS, during the last ten years. We found 28 cases that were available to study. RESULTS: Mean age was 37 years old (SD 17.2). Fifteen patients were female (54%) and 13 were male (46%). Nine patients (32%) were preceded by a superior via infection, 5 (18%) by a diarrhea illness and 14 patients had not a predisposing factor. The duration of symptoms before diagnostic has a median of 7 days (2-15). Twenty-six patients (93%) had an ascending paralysis and 18 had paresthesias (64%). The most frequent subtype was acute inflammatory-demyelinating polyneuropathy (AIDP) in 18 patients (64%), acute motor-sensory axonal neuropathy (AMSAN) in 5 (18%), acute motor axonal neuropathy (AMAN) in 3 (11%) and 2 patients (7%) had the Fisher-Miller syndrome. Fifteen patients (54%) developed respiratory involvement requiring mechanical ventilation. Twenty-four patients (86%) had cerebrospinal fluid proteins elevated. Twenty patients (72%) had a total recovery, 6 (21%) had a partial recovery and 2 had not any response (7%). DISCUSSION: GBS is a particularly highstakes illness in that its onset is sudden and paralysis is frequently extreme (requiring assisted respiration), however, as many as 85% of those affected can be expected to make an excellent recovery. In our study the majority of patients (54%) develop respiratory involvement requiring mechanical ventilation but in this group the majority had a favorable outcome (71%).

Adult↗
PubMed1988

Upper respiratory tract involvement in sarcoidosis and its management.

Of some 750 sarcoidosis patients, 27 were found to have involvement of their nasal mucosa. Most had multisystem disease, which was usually chronic. Nasal stuffiness or blockage and crusting were the major symptoms, and were usually present at the first presentation with sarcoidosis. The larynx was involved in five cases. The Kveim test was positive in twelve of the fourteen patients in whom it was performed, serum angiotensin converting enzyme was frequently elevated and sinus radiographs were often abnormal. Topical medication improved symptoms in some patients, but the majority required systemic corticosteroids. It was possible to withdraw medication completely after seven years in only one patient. Relapse was encountered during reduction of dosage in other patients. Random biopsy of macroscopically normal nasal mucosa did not yield histological support for a diagnosis of sarcoidosis in twelve out of thirteen patients, but upper respiratory tract lymphoid tissue may contain granulomas in patients with sarcoidosis.

Adenoids↗
PubMed2004

Characteristics and acute rehabilitation of Guillain-Barré syndrome in Singapore.

INTRODUCTION: The objectives of this study are to describe the demographics, clinical characteristics, complications and functional outcomes in patients with Guillain-Barr é syndrome (GBS) or the Miller-Fisher syndrome (MFS) variant admitted to our institution. We also aim to identify prognostic outcome indicators. MATERIALS AND METHODS: A retrospective review of the case records of all patients discharged from our hospital with a diagnosis of GBS or MFS over a 2- year period was performed. The clinical characteristics charted included the time of symptom onset to nadir. The Modified Barthel Index (MBI) and Expanded Grading Scale (EGS) for GBS were the functional outcome measures used. RESULTS: Thirty-one cases were reviewed and 8 (25.8 %) had the MFS variant. Twenty-two (71 %) patients were male, with a mean age of 42.3 years. Weakness and numbness (74 %) were the most common initial symptoms; 9 (29 %) patients were paraparetic and 7 (22.6 %) were tetraparetic. Ten (32.3 %) patients had respiratory involvement and 8 (25.8 %) had urinary retention. Intravenous immunoglobulin (IVIG) was prescribed in 13 (41.9 %) patients. The mean duration to disease nadir was 8.1 days. The mean MBI scores at nadir and discharge were 54.7 and 77.3, respectively, and this gain was highly significant (P <0.01). The majority (84 %) of patients were employed at admission and although most returned to work, 63 % (17/27) of the patients had residual symptoms or signs 3 months after discharge. CONCLUSION: The clinical characteristics and complication frequency closely follows that previously described in Western populations, although our cohort was younger and had a higher proportion of the MFS variant. Predictors of a poorer functional outcome include a high EGS score at nadir, tetraparesis, respiratory involvement, urinary retention and the need for nasogastric enteral feeding. Patients who had MFS or received IVIG had greater functional gains. Good functional outcomes occurred in a large majority of patients.

Adult↗
PubMed1993

Contractile effects of nucleotides in guinea pig isolated, perfused trachea: involvement of respiratory epithelium, prostanoids and Na+ and Cl- channels.

ATP and UTP contracted guinea pig isolated, perfused trachea and were more potent when applied to the mucosal (intraluminal, IL) surface than when applied to the serosal (extraluminal, EL) surface. IL ATP and IL UTP were equipotent (ATP approximately UTP); EL ATP was 7-fold more potent than EL UTP (ATP > UTP). beta, gamma-Methylene ATP was nearly devoid of activity. Epithelium (Epi) removal decreased IL ATP potency and EL and IL maximum response magnitude, but elevated the IL UTP maximum response. In the presence of EL and IL indomethacin (3 x 10(-6) M; +/- Epi) to inhibit cyclo-oxygenase, or beta, gamma-methylene ATP (10(-4) M) to desensitize receptors, contractions to ATP were abolished, but those to UTP were not. Cl- channel blockade with 4,4'-diisothiocyano-2,2'-stilbene disulfonate (DIDS; 10(-4) M; +/- Epi) and sodium channel blockade with amiloride (10(-4) M; +/- Epi) antagonized contractions to EL and IL ATP and UTP. DIDS and amiloride did not inhibit contractions to methacholine; IL reactivity to methacholine was potentiated by indomethacin and Epi removal. Our findings indicate that the Epi facilitates contraction to ATP, which involves an atypical P2 purinoceptor, prostanoids, and Na+ and Cl- channels. Contractile responses to UTP involve a different receptor, and are neither facilitated by the Epi nor mediated by prostanoids, but involve these channels.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2004

Novel, attached, sulfur-oxidizing bacteria at shallow hydrothermal vents possess vacuoles not involved in respiratory nitrate accumulation.

Novel, vacuolate sulfur bacteria occur at shallow hydrothermal vents near White Point, Calif. There, these filaments are attached densely to diverse biotic and abiotic substrates and extend one to several centimeters into the surrounding environment, where they are alternately exposed to sulfidic and oxygenated seawater. Characterizations of native filaments collected from this location indicate that these filaments possess novel morphological and physiological properties compared to all other vacuolate bacteria characterized to date. Attached filaments, ranging in diameter from 4 to 100 microm or more, were composed of cylindrical cells, each containing a thin annulus of sulfur globule-filled cytoplasm surrounding a large central vacuole. A near-complete 16S rRNA gene sequence was obtained and confirmed by fluorescent in situ hybridization to be associated only with filaments having a diameter of 10 microm or more. Phylogenetic analysis indicates that these wider, attached filaments form within the gamma proteobacteria a monophyletic group that includes all previously described vacuolate sulfur bacteria (the genera Beggiatoa, Thioploca, and Thiomargarita) and no nonvacuolate genera. However, unlike for all previously described vacuolate bacteria, repeated measurements of cell lysates from samples collected over 2 years indicate that the attached White Point filaments do not store internal nitrate. It is possible that these vacuoles are involved in transient storage of oxygen or contribute to the relative buoyancy of these filaments.

Bacteria↗
PubMed1987

[Characteristics of respiratory functional involvement in MacLeod's syndrome (or Swyer-James syndrome)].

MacLeod's syndrome (Swyer-James' syndrome in the child) is a radiologic entity: hyperlucency of one or several lobes, or even of one lung, scarce hilar shadow on the same side as the abnormal transradiency, and barely visible arterial network on the abnormal side of the thorax. Distal bronchiectases (bronchography) and abnormal distal bronchi (necropsy) suggest that this disease may be due to bronchiolitis in childhood. An obstructive pulmonary disorder, assessed by pulmonary function tests, has been described in this syndrome. However, neither the prevalence nor the severity or evolution of the obstructive defect are known. We have studied two such patients for 5 and 12 years respectively: during this long follow-up period the obstructive disorder, albeit severe, remained stable. We have also analysed the 75 cases in the literature in which pulmonary function tests are available and comparable. We have been able to show that (1) an obstructive disorder is frequent in MacLeod's syndrome, (2) the severity of this disorder differs markedly between patients, and (3) this airflow limitation is probably stable on a long-term basis. These findings are compatible with the pathogenetic hypothesis at present accepted, ie bronchiolitis during childhood, and suggest that the inflammatory bronchial disease may have been generalized in many such patients.

Adult↗
PubMed2006

Anti-inflammatory effect of interleukin-10 on human neutrophil respiratory burst involves inhibition of GM-CSF-induced p47PHOX phosphorylation through a decrease in ERK1/2 activity.

Interleukin-10 (IL-10) exerts its anti-inflammatory properties by down-regulating polymorphonuclear neutrophil (PMN) functions such as reactive oxygen species (ROS) production via NADPH oxidase. The molecular mechanisms underlying this process are unclear. Partial phosphorylation of the NADPH oxidase cytosolic component p47(PHOX) induced by proinflammatory cytokines, such as granulocyte-macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-alpha, is essential for priming ROS production by PMN. The aim of this study was to determine whether IL-10 inhibits GM-CSF- and TNFalpha-induced p47(PHOX) phosphorylation and to investigate the molecular mechanisms involved in this effect. We found that IL-10 selectively inhibited GM-CSF- but not TNFalpha-induced p47PHOX phosphorylation in a concentration-dependent manner. As GM-CSF-induced p47PHOX phosphorylation is mediated by extracellular signal-regulated kinase 1/2 (ERK1/2), we tested the effect of IL-10 on this pathway. We found that IL-10 inhibited GM-CSF-induced ERK1/2 activity in an immunocomplex kinase assay. This inhibitory effect was confirmed by analyzing the phosphorylation status of the endogenous substrate of ERK1/2, p90RSK, in intact PMN. Furthermore, IL-10 decreased ROS production by adherent GM-CSF-treated PMN in keeping with the higher ROS production observed in whole blood from IL-10 knockout mice compared to their wild-type counterparts. Together, these results suggest that IL-10 inhibits GM-CSF-induced priming of ROS production by inhibiting p47PHOX phosphorylation through a decrease in ERK1/2 activity. This IL-10 effect could contribute to the tight regulation of NADPH oxidase activity at the inflammatory site.

Granulocyte-Macrophage Colony-Stimulating Factor↗