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1.
Dermatol Online J ; 25(6)2019 Jun 15.
Article in English | MEDLINE | ID: mdl-31329385

ABSTRACT

BACKGROUND: Malacoplakia is a rare acquired, infection-related granulomatous disorder, that may affect many systems, but typically occurs in the urinary tract. Cutaneous involvement is less prevalent, and most commonly presents with a perianal or genital region localization. Cutaneous malacoplakia is believed to be caused by an acquired bactericidal defect of macrophages in the setting of chronic infections and immunocompromised states. A diagnosis of cutaneous malacoplakia should be considered when encountering non-specific granulomatous lesions that are refractory to treatment. Histologic findings are marked by the presence of foamy macrophages containing the pathognomonic Michaelis-Gutman bodies. OBJECTIVES: The aim of this review is to discuss the current perspectives on the pathophysiology, clinical features, diagnosis, and treatment of this disease. We would also like to emphasize that the integration of clinical information, microscopic findings, and exclusion of other cutaneous granulomatous processes is necessary to accurately diagnose this exceedingly rare disease and provide opportunity for therapeutic intervention. PATIENTS/METHODS: Data for this work were collected from the published literature and textbooks. RESULTS: Combined surgical excision and protracted antibiotic courses appear to have the highest success rate. Antibiotics should be culture specific, but drugs that easily permeate the macrophages appear to be the best choice.


Subject(s)
Macrophages/pathology , Malacoplakia/pathology , Skin Diseases, Bacterial/pathology , Anti-Bacterial Agents/therapeutic use , Dermatologic Surgical Procedures , Granuloma/pathology , Humans , Macrophages/immunology , Malacoplakia/diagnosis , Malacoplakia/immunology , Malacoplakia/therapy , Phagocyte Bactericidal Dysfunction/immunology , Skin Diseases, Bacterial/diagnosis , Skin Diseases, Bacterial/immunology , Skin Diseases, Bacterial/therapy
2.
Cell Mol Life Sci ; 69(1): 7-15, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22083605

ABSTRACT

Chronic granulomatous disease (CGD) is an uncommon congenital immunodeficiency seen approximately in 1 of 250,000 individuals. It is caused by a profound defect in a burst of oxygen consumption that normally accompanies phagocytosis in all myeloid cells (neutrophils, eosinophils, monocytes, and macrophages). This "respiratory burst" involves the catalytic conversion of molecular oxygen to the oxygen free-radical superoxide, which in turn gives rise to hydrogen peroxide, hypochlorous acid, and hydroxyl radicals. These oxygen derivatives play a critical role in the killing of pathogenic bacteria and fungi. As a result of the failure to activate the respiratory burst in their phagocytes, the majority of CGD patients suffer from severe recurrent infections and rather unexplained prolonged inflammatory reactions that may result in granulomatous lesions. Both may cause severe organ dysfunction depending on the tissues involved. Preventive measures as well as rapid (invasive) diagnostic procedures are required to successfully treat CGD. Hematopoietic stem cell transplantation may be a serious option in some of the patients.


Subject(s)
Granulomatous Disease, Chronic , Inflammation/immunology , Kynurenine/metabolism , NADPH Oxidases , T-Lymphocytes, Regulatory , Animals , Female , Granulomatous Disease, Chronic/genetics , Granulomatous Disease, Chronic/immunology , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Inflammation/metabolism , Interleukin-17/immunology , Interleukin-17/metabolism , Kynurenine/immunology , Male , Mice , Models, Animal , NADPH Oxidases/deficiency , NADPH Oxidases/immunology , NF-E2-Related Factor 2/deficiency , NF-E2-Related Factor 2/immunology , Phagocyte Bactericidal Dysfunction/immunology , Phagocytes/immunology , Phagocytes/pathology , Phagocytosis/physiology , Respiratory Burst/immunology , Superoxides/immunology , Superoxides/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Transforming Growth Factor beta/immunology , Transforming Growth Factor beta/metabolism
3.
J Clin Immunol ; 31(3): 297-308, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21243521

ABSTRACT

Two hundred and one patients have been diagnosed with primary immunodeficiency diseases (PIDs) in our center from January 2004 to December 2009. The male-to-female ratio was 5.29:1. Spectrums of PIDs were as follows: predominantly antibody deficiency disease was the most common category (94 patients, 48.2%), followed by other well-defined immunodeficiency syndromes (40 patients, 20.5%), combined T and B cell immunodeficiencies (33 patients, 16.9%), congenital defects of phagocyte number and/or function (21 patients, 10.8%), and diseases of immune dysregulation (six patients, 3.1%). Agammaglobulinemia was the most frequent disease type. The median of diagnosis lag was 18.0 months. Pneumonia was the most common manifestation of PID patients. Some manifestations were prone to concentrate in certain diseases. As for therapy, 99 patients (50.8%) received intravenous immunoglobulin replacement therapy; 13 patients received hematopoietic stem cell transplantation and nine of them were still alive. In this study, we sought to describe and analyze the distribution, clinical features, and therapy methods of PIDs among children diagnosed in our country and to compare with reports from other countries and regions.


Subject(s)
Agammaglobulinemia/immunology , Common Variable Immunodeficiency/immunology , Immunoglobulins/pharmacology , Phagocyte Bactericidal Dysfunction/immunology , Severe Combined Immunodeficiency/immunology , Adolescent , Agammaglobulinemia/epidemiology , Agammaglobulinemia/mortality , Agammaglobulinemia/pathology , Agammaglobulinemia/therapy , Anti-Bacterial Agents/pharmacology , Asian People , Child , Child, Preschool , Common Variable Immunodeficiency/epidemiology , Common Variable Immunodeficiency/mortality , Common Variable Immunodeficiency/pathology , Common Variable Immunodeficiency/therapy , Consanguinity , Family , Female , Hematopoietic Stem Cell Transplantation , Humans , Immunoglobulin Isotypes/analysis , Immunoglobulins/immunology , Incidence , Infant , Infant, Newborn , Longitudinal Studies , Male , Phagocyte Bactericidal Dysfunction/epidemiology , Phagocyte Bactericidal Dysfunction/mortality , Phagocyte Bactericidal Dysfunction/pathology , Phagocyte Bactericidal Dysfunction/therapy , Retrospective Studies , Severe Combined Immunodeficiency/epidemiology , Severe Combined Immunodeficiency/mortality , Severe Combined Immunodeficiency/pathology , Severe Combined Immunodeficiency/therapy , Survival Rate
5.
J Leukoc Biol ; 76(3): 648-56, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15240745

ABSTRACT

Leukocytes express both urokinase-type plasminogen activator (uPA) and the urokinase receptor (uPAR, CD87). We have shown that neutrophil recruitment to the lung during P. aeruginosa pneumonia is impaired in uPAR-deficient (uPAR-/-) mice but is normal in uPA-/- mice. However, both uPA-/- mice and uPAR-/- mice have impaired lung clearance of P. aeruginosa compared with wild-type (WT) mice. To determine the role of uPA and uPAR in antibacterial host defense, we compared neutrophil bacterial-phagocytosis, respiratory burst, and degranulation among uPA-/-, uPAR-/-, and WT mice. Neutrophil phagocytosis was significantly diminished comparing uPA-/- and uPAR-/- mice with WT mice at all time points. The generation of superoxide by both uPA-/- and uPAR-/- neutrophils was about half of that seen in WT neutrophils. Degranulation of azurophilic granules was significantly diminished in uPA-/- neutrophils compared with either uPAR-/- or WT neutrophils. By contrast, agonist-stimulated release of specific granules was not diminished in either uPA-/- or uPAR-/- mice compared with WT. We conclude that the uPA/uPAR system modulates several of the crucial steps in neutrophil activation that result in bacterial killing and effective innate host defense.


Subject(s)
Bacterial Infections/immunology , Chemotaxis, Leukocyte/immunology , Immunologic Deficiency Syndromes/enzymology , Neutrophils/immunology , Receptors, Cell Surface/deficiency , Urokinase-Type Plasminogen Activator/deficiency , Animals , Chemotaxis, Leukocyte/genetics , Cytoplasmic Granules/metabolism , Immunity, Innate/genetics , Immunity, Innate/immunology , Immunologic Deficiency Syndromes/genetics , Mice , Mice, Knockout , Neutrophils/enzymology , Neutrophils/microbiology , Phagocyte Bactericidal Dysfunction/genetics , Phagocyte Bactericidal Dysfunction/immunology , Phagocytosis/immunology , Pneumonia, Bacterial/immunology , Pseudomonas Infections/immunology , Pseudomonas aeruginosa/immunology , Receptors, Cell Surface/genetics , Receptors, Urokinase Plasminogen Activator , Superoxides/metabolism , Urokinase-Type Plasminogen Activator/genetics
6.
Rev. cuba. hematol. inmunol. hemoter ; 20(1)ene.-abr. 2004. tab
Article in Spanish | CUMED | ID: cum-24118

ABSTRACT

Se realiza una revisión sobre los defectos presentes en la función de los fagocitos que provocan trastornos inmunitarios. Se exponen las características clínicas, moleculares e inmunológicas que caracterizan a cada desorden fagocítico, así como los métodos de laboratorio utilizados para el diagnóstico de estos. Se hace referencia a los tratamientos terapéuticos efectivos que eliminan o atenúan las manifestaciones clínicas de cada defecto de la fagocitosis estudiado.(AU)


Subject(s)
Humans , Phagocytosis/genetics , Phagocytosis/immunology , Phagocyte Bactericidal Dysfunction/diagnosis , Phagocyte Bactericidal Dysfunction/genetics , Phagocyte Bactericidal Dysfunction/immunology
7.
Rev. cuba. hematol. inmunol. hemoter ; 20(1)ene.-abr. 2004. tab
Article in Spanish | LILACS | ID: lil-394349

ABSTRACT

Se realiza una revisión sobre los defectos presentes en la función de los fagocitos que provocan trastornos inmunitarios. Se exponen las características clínicas, moleculares e inmunológicas que caracterizan a cada desorden fagocítico, así como los métodos de laboratorio utilizados para el diagnóstico de estos. Se hace referencia a los tratamientos terapéuticos efectivos que eliminan o atenúan las manifestaciones clínicas de cada defecto de la fagocitosis estudiado.


Subject(s)
Humans , Phagocyte Bactericidal Dysfunction/diagnosis , Phagocyte Bactericidal Dysfunction/genetics , Phagocyte Bactericidal Dysfunction/immunology , Phagocytosis
9.
J Immunol ; 169(6): 3223-31, 2002 Sep 15.
Article in English | MEDLINE | ID: mdl-12218141

ABSTRACT

This study defines the molecular basis for defects in innate immunity involving neutrophils during cecal ligation/puncture (CLP)-induced sepsis in rats. Blood neutrophils from CLP rats demonstrated defective phagocytosis and defective assembly of NADPH oxidase, the latter being due to the inability of p47(phox) to translocate from the cytosol to the cell membrane of neutrophils after cell stimulation by phorbol ester (PMA). The appearance of these defects was prevented by in vivo blockade of C5a in CLP rats. In vitro exposure of neutrophils to C5a led to reduced surface expression of C5aR and defective assembly of NADPH oxidase, as defined by failure in phosphorylation of p47(phox) and its translocation to the cell membrane, together with failure in phosphorylation of p42/p44 mitogen-activated protein kinases. These data identify a molecular basis for defective innate immunity involving neutrophils during sepsis.


Subject(s)
Complement C5a/pharmacology , Neutrophils/immunology , Respiratory Burst/immunology , Sepsis/immunology , Animals , Antigens, CD/analysis , Cecum , Complement C5a/immunology , Complement C5a/metabolism , Humans , Hydrogen Peroxide/metabolism , Immune Sera/administration & dosage , Immunity, Innate , Immunization, Passive , Ligation , MAP Kinase Kinase 1 , Male , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinase Kinases/metabolism , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/metabolism , NADPH Oxidases/antagonists & inhibitors , NADPH Oxidases/metabolism , Neutrophil Activation/drug effects , Neutrophil Activation/immunology , Neutrophils/drug effects , Neutrophils/enzymology , Neutrophils/metabolism , Phagocyte Bactericidal Dysfunction/immunology , Phosphoproteins/antagonists & inhibitors , Phosphoproteins/metabolism , Phosphorylation/drug effects , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein Serine-Threonine Kinases/metabolism , Punctures , Rats , Rats, Long-Evans , Receptor, Anaphylatoxin C5a , Receptors, Complement/analysis , Receptors, Complement/antagonists & inhibitors , Sepsis/pathology , Sepsis/prevention & control , Signal Transduction/immunology , Tetradecanoylphorbol Acetate/antagonists & inhibitors , Tetradecanoylphorbol Acetate/pharmacology
10.
Probl Tuberk ; (5): 46-8, 2002.
Article in Russian | MEDLINE | ID: mdl-12164122

ABSTRACT

Stress substantially modulates the mononuclear phagocytic system (its center and periphery), the time of changes in granuloma formation in animals infected with BCG vaccine. This determines the specific features of development of vaccine-induced granulomatous inflammation as a reflection of changes in the host's resistance system and possibly mycobacteria. An additional influence (to Mycobacteria tuberculosis) of stresses during 30 days enhances destructive processes in the hepatic parenchyma.


Subject(s)
BCG Vaccine/immunology , Liver Diseases/physiopathology , Phagocyte Bactericidal Dysfunction/immunology , Stress, Psychological/immunology , Stress, Psychological/prevention & control , Animals , Bone Marrow/immunology , Liver Diseases/etiology , Mice , Monocytes/immunology , Phagocyte Bactericidal Dysfunction/etiology , Stress, Psychological/psychology
11.
Ter Arkh ; 73(4): 55-9, 2001.
Article in Russian | MEDLINE | ID: mdl-11494450

ABSTRACT

AIM: To evaluate alterations in the immune system (IS) in patients with different forms of secondary immunodeficiency and design of differentiated programs of reestablishment of defective functions depending on pathogenetically important type of deficiency of immunocompetent cells. MATERIALS AND METHODS: Clinicoimmunological examination was made in 678 patients with complicated course of infectious-inflammatory diseases. Immunotropic medicines and physicochemical impacts were used in accordance with types of disorders in the system of immune homeostasis. RESULTS: There was a pathogenetic heterogeneity of IS disorders in complicated course of infectious-inflammatory diseases: generalized forms of infection (bacterial shock, sepsis) are in 75% of cases associated with deficiency of effector functions of peripheral blood polymorphonuclear leukocytes of the second-third degree, progressive fall in production of IgG immunoglobulins (42%), cellular-humoral immunodeficiency (92%). In lingering acute inflammatory diseases activation of phagocytosis occurred in 30%, IgG and/or IgM rise was in 50%, phagocytic function deficiency occurred in 48%, low production of immunoglobulins in 24%, humoral-cellular immunodeficiency in 62%. Purulent infection is associated with secondary cellular-humoral immunodeficiency, lowering of the immunoregulatory index (47%), phagocytic function deficiency (up to 35%), hyperproduction of IgM. Recurrent bacterial-viral diseases form in immunocompromised patients with T-lymphocytopenia (56%) and cellular-humoral immunodeficiency (30%). CONCLUSION: Protracted chronic inflammatory diseases are characterized by variability of changes in the immune systems. Combined types of disorders were found in 52% of the examinees. Pathogenetic heterogeneity of the disorders are determined by concomitant and previous diseases, occupational hazards and intoxication, environmental conditions, etc. CONCLUSION: Immunocorrective therapy in secondary immunodeficiency is conducted with allowances for pathogenetically essential types of disorders in the system of immune homeostasis, clinical variant of complication of inflammatory process under control of immunogram.


Subject(s)
Immunologic Deficiency Syndromes/diagnosis , Immunologic Deficiency Syndromes/therapy , Infections/immunology , Inflammation/immunology , Acute Disease , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/therapeutic use , Antibody Formation , Biomarkers , Bronchitis/immunology , Chronic Disease , Cytokines/administration & dosage , Cytokines/therapeutic use , Drug Combinations , Fluorescent Antibody Technique, Indirect , Homeostasis , Humans , Immunity, Cellular , Immunocompromised Host , Immunoglobulins/deficiency , Immunologic Deficiency Syndromes/etiology , Immunologic Factors/administration & dosage , Immunologic Factors/therapeutic use , Interferon Type I/administration & dosage , Interferon Type I/therapeutic use , Oligopeptides/administration & dosage , Oligopeptides/therapeutic use , Phagocyte Bactericidal Dysfunction/immunology , Phagocytes/immunology , Pneumonia/immunology , Recurrence , Rosette Formation , Shock, Septic/immunology , Suppuration/immunology , T-Lymphocytes/immunology , Time Factors , Virus Diseases/immunology
12.
Microbes Infect ; 1(8): 581-7, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10611734

ABSTRACT

Human phagocytes (polymorphonuclear neutrophils and monocytes) play a critical role in host defense against invading microorganisms. Recent studies reported that circulating phagocytes undergo a final maturation process, in particular in terms of oxidative burst, during extravasation and migration to local sites of inflammation. This process is known as priming. We report here on a nine-year-old boy with successive disseminated infections due to intracellular microorganisms (Mycobacterium bovis, BCG, and Salmonella typhimurium). No T- or B-cell quantitative or qualitative defects were found. Polymorphonuclear neutrophil (PMN) migration and NADPH oxidase in PMNs and monocytes stimulated with various agents at optimal concentrations were normal, ruling out a leukocyte adhesion deficiency syndrome, a Chediak Higashi syndrome, and a chronic granulomatous disease. Nevertheless, the patient's PMNs and monocytes showed defective priming capacity, as measured by H(2)O(2) production after pretreatment with LPS (5 microg/mL for 30 min), TNFalpha (100 units/mL for 30 min), or IL-8 (50 ng/mL for 30 min) in response to bacterial N-formyl peptides (fMLP 10(-6) M for 5 min). In these conditions, H(2)O(2) production of PMNs and monocytes from the patient did not exceed that of the samples treated with fMLP or LPS alone, while the controls strongly produced H(2)O(2). Moreover, monocytes from the patient showed an impaired capacity to kill S. typhimurium in vitro. Such an impairment could be related at least in part to the priming deficiency of phagocyte oxidative burst. This case suggests, for the first time, that in vivo priming processes are critical in host defence against intracellular pathogens.


Subject(s)
Monocytes/metabolism , Neutrophils/metabolism , Respiratory Burst , Adult , Cells, Cultured , Chemotaxis, Leukocyte/drug effects , Child , Consanguinity , Cytochrome c Group/metabolism , Cytokines/pharmacology , Female , Genes, Recessive , Humans , Hydrogen Peroxide/blood , Hydrogen Peroxide/metabolism , Lipopolysaccharides/pharmacology , Male , Monocytes/drug effects , Monocytes/microbiology , Monocytes/pathology , Mycobacterium bovis/immunology , Mycobacterium bovis/physiology , N-Formylmethionine Leucyl-Phenylalanine/pharmacology , NADPH Oxidases/metabolism , Neutrophils/drug effects , Neutrophils/microbiology , Neutrophils/pathology , Phagocyte Bactericidal Dysfunction/enzymology , Phagocyte Bactericidal Dysfunction/immunology , Phagocyte Bactericidal Dysfunction/metabolism , Phagocyte Bactericidal Dysfunction/pathology , Recurrence , Respiratory Burst/drug effects , Salmonella Infections/enzymology , Salmonella Infections/immunology , Salmonella Infections/metabolism , Salmonella Infections/pathology , Salmonella typhimurium/immunology , Salmonella typhimurium/physiology
13.
14.
Orv Hetil ; 134(32): 1753-6, 1993 Aug 08.
Article in Hungarian | MEDLINE | ID: mdl-8351139

ABSTRACT

Leukocyte adhesion defect (LAD) is an inherited defect of phagocytic function. This disorder is characterised by delayed separation of the umbilical cord, severe recurrent bacterial infections, impaired formation of pus, and high leukocyte counts. The granulocytes have severe defect in their chemotactic mobility and endocytosis. The disease is attributed to the absence of the leukocyte adhesion molecules. (CD11/CD18), which can be verified with monoclonal antibodies. The authors describe the disease-process of the first patient diagnosed in Hungary. Perinatally the omphalitis, periumbilical abscess and periproctal abscess leading to rectovaginal fistula, in the first months the otitis, mastoiditis, and expressed leukocytosis referred to the impaired function of phagocytic cells, which was verified by laboratory tests as well. The decreased inflammation and cicatrization were also striking. This severe form of LAD can be cured only by bone marrow transplantation with preliminary sanitation of the foci of infection. It took about six months. Unfortunately, the patient died of sepsis immediately before transplantation.


Subject(s)
Bacterial Infections/immunology , Immunologic Deficiency Syndromes/genetics , Phagocyte Bactericidal Dysfunction/genetics , Receptors, Leukocyte-Adhesion/immunology , Antibodies, Monoclonal/immunology , Bone Marrow Transplantation , Chemotaxis , Female , Humans , Hungary , Infant, Newborn , Leukocytosis/immunology , Phagocyte Bactericidal Dysfunction/immunology , Phagocyte Bactericidal Dysfunction/therapy , Pulmonary Circulation , Recurrence
15.
Ginekol Pol ; 64(4): 193-6, 1993 Apr.
Article in Polish | MEDLINE | ID: mdl-8282242

ABSTRACT

Phagocytosis and bactericidal capacity of polymorphonuclear neutrophils (PMN) obtained from umbilical venous blood was estimated in 30 neonates and their mothers by the use of fluorochrome microassay of Pantazis and Kniker. Phagocytosis of Staphylococcus was similar in both groups and controls, while intracellular bacteria killing was significantly impaired in PMN obtained from the neonates. These results may indicate that increased susceptibility to infection observed in neonates may be partly caused by PMN function impairment.


Subject(s)
Infant, Newborn, Diseases/immunology , Neutrophils/immunology , Phagocyte Bactericidal Dysfunction/immunology , Pregnancy/immunology , Adult , Blood Bactericidal Activity , Female , Humans , Infant, Newborn , Phagocytosis/immunology , Reference Values , Staphylococcus/immunology
16.
J Surg Oncol ; 51(3): 159-63, 1992 Nov.
Article in English | MEDLINE | ID: mdl-1331619

ABSTRACT

We examined whether or not preoperative impaired bactericidal activities of polymorphonuclear neutrophils (PMN) are associated with infections following surgery for esophageal cancer. Intracellular killing (KI), superoxide anion-producing capacity (SOP), and myeloperoxidase (MPO) activity were measured in 22 patients with esophageal cancer, 27 with gastric cancer, and 13 age-matched controls. The average level of KI was significantly depressed in patients with esophageal cancer or with gastric cancer, to a similar extent, compared to findings in controls, but SOP was not. In esophageal cancer patients, the SOP level was significantly higher in those with postoperative septic complications than in those without such problems, whereas the KI level was depressed to a similar extent in both. Therefore, a depression of KI with elevation of SOP of PMN may serve to predict complications of infection following surgery in patients with esophageal cancer.


Subject(s)
Bacterial Infections/immunology , Esophageal Neoplasms/surgery , Neutrophils/physiology , Phagocyte Bactericidal Dysfunction/immunology , Postoperative Complications/immunology , Adult , Aged , Aged, 80 and over , Bacteria/immunology , Female , Humans , Male , Middle Aged , Neutrophils/metabolism , Peroxidase/metabolism , Superoxides/metabolism
17.
J Lab Clin Med ; 117(3): 181-93, 1991 Mar.
Article in English | MEDLINE | ID: mdl-2002275

ABSTRACT

Although several studies have reported abnormal immune clearance in murine models of systemic lupus erythematosus (SLE), a consistent defect in mononuclear phagocyte function in SLE-prone mice has not been described. To evaluate the mechanism(s) of immune clearance in murine SLE, we applied the technique of kinetic analysis to clearance studies of radiolabeled, immunoglobulin-sensitized red blood cells in normal BALB/c and autoimmune BXSB, MRL-lpr/lpr, New Zealand black (NZB) and New Zealand black/white (NZB/W) mice. Clearance studies were performed in 4-week-old to 18-month-old mice with a complement-fixing rabbit IgG antimouse red blood cell antibody. Four clearance rate constants governing complement- and Fc-mediated clearance function were evaluated: complement-mediated sequestration (k1), C3b deactivation and release (k2), complement-dependent phagocytosis (k4), and Fc-mediated sequestration and phagocytosis (k3). BXSB male, MRL-lpr/lpr female and male, NZB female, and NZB/W female and male mice all had significantly decreased Fc-mediated clearance function (k3) when compared with control BALB/c mice (p less than 0.0001). This defect in Fc-mediated clearance was present in all four strains of autoimmune mice by 6 months of age and preceded the onset of serologic and clinical disease activity in NZB mice. Abnormal complement-mediated clearance was detected in MRL-lpr/lpr female and male mice, NZB female, and NZB/W female and male mice, but not in BXSB mice. In MRL-lpr/lpr mice decreased complement-mediated sequestration (k1, p less than 0.0001) and complement-dependent phagocytosis (k4, p less than 0.0001) were present as early as 4 weeks of age. In contrast, the change in complement-mediated clearance in NZB and NZB/W mice was characterized by decreased C3b deactivation and release (k2, p less than 0.001) and resulted in an enhanced early phase of clearance. Decreased k2 values in New Zealand mice occurred as early as 2 months of age, preceding serologic and clinical disease activity as well as decreased Fc receptor function. These studies demonstrated an early, progressive, and uniform defect in Fc-mediated clearance in the four murine strains of SLE studied. Complement-mediated clearance, however, varied considerably in lupus-prone mice, ranging from severe impairment in MRL-lpr/lpr to normal function in BXSB and accelerated clearance in NZB and NZB/W mice. Accelerated clearance in New Zealand mice was characterized by decreased C3b deactivation and release of antibody sensitized cells, which in turn led to increased phagocytosis of sensitized cells sequestered by complement-dependent processes.


Subject(s)
Lupus Erythematosus, Systemic/physiopathology , Phagocyte Bactericidal Dysfunction/metabolism , Animals , Antibodies/immunology , Autoimmunity/immunology , Complement Activation , Complement System Proteins/immunology , Complement System Proteins/physiology , Erythrocytes/immunology , Female , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred NZB , Mice, Inbred Strains , Phagocyte Bactericidal Dysfunction/immunology
18.
Br J Haematol ; 77(2): 150-7, 1991 Feb.
Article in English | MEDLINE | ID: mdl-1672257

ABSTRACT

The role of leucocyte integrins in phagocyte function has been studied by comparing normal neutrophils with those from a patient with partial leucocyte adhesion deficiency (LAD), in whom the levels of CD11b and CD11c were 10% of controls, whereas CD11a levels were normal. Unstimulated LAD neutrophils exhibited defective adhesion to plastic (4.4 +/- 1.5% cf. 14.4 +/- 3.8% in controls), but not to human umbilical vein endothelial cells (HUVECs). The adhesion to HUVECs could be further upregulated by granulocyte-macrophage colony stimulating factor (GM-CSF), but not by 12-O-tetradecanoylphorbol 13-acetate (TPA) which, in normal cells, is a more potent 'pro-adhesive agonist'. The normal neutrophil-endothelial interaction induced by GM-CSF in LAD neutrophils was confirmed in vivo when administration of GM-CSF resulted in rapid phagocyte margination. Neutrophil migration and phagocytosis/killing were defective in LAD neutrophils, and some improvement in phagocytosis/killing was seen following in vivo administration of GM-CSF. These studies illustrate that the degree to which the leucocyte integrins mediate adherence-related phagocyte functions varies not only with the particular function, but also with the conditions of stimulation. High levels of CD11b and CD11c expression appear not to be required for unstimulated or GM-CSF-stimulated neutrophil-endothelial interactions, either in vitro or in vivo. Other neutrophil functions, on the other hand, such as migration and phagocytosis/killing are much more dependent on the leucocyte integrins.


Subject(s)
Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Integrins/immunology , Phagocyte Bactericidal Dysfunction/immunology , Phagocytosis/immunology , Antigens, CD/analysis , Antigens, Differentiation/analysis , CD11 Antigens , Cell Adhesion/immunology , Cell Movement/immunology , Child , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Humans , Male , Neutrophils/immunology , Phagocyte Bactericidal Dysfunction/therapy
20.
Ugeskr Laeger ; 152(34): 2417-20, 1990 Aug 20.
Article in Danish | MEDLINE | ID: mdl-2205959

ABSTRACT

Since 1972, 150 cases of the hyper-IgE-syndrome have been reported. The clinical manifestations are rather homogeneous with recurrent subcutaneous infections and infections in the respiratory tract, mostly with juvenile onset. Laboratory tests show minor eosinophilia and elevated immunoglobulin E-levels are always seen, partly specific to Staphylococcus aureus. Also varying decreases of polymorphonuclear leucocyte-chemotactic response are seen. There is no specific treatment of the disorder, only treatment of current infections has proved valuable. A case history is presented.


Subject(s)
Immunoglobulin E/analysis , Job Syndrome/immunology , Phagocyte Bactericidal Dysfunction/immunology , Humans , Male , Middle Aged
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