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Journal of Leukocyte Biology May 2007Immune complex (IC)-induced inflammation is mediated by inflammatory cell infiltration, a process that is highly regulated by expression of multiple adhesion molecules....
Immune complex (IC)-induced inflammation is mediated by inflammatory cell infiltration, a process that is highly regulated by expression of multiple adhesion molecules. The roles and interactions of ICAM-1 and VCAM-1, the major regulators of leukocyte firm adhesion, were examined in the cutaneous reverse-passive Arthus reaction using ICAM-1-deficient (ICAM-1-/-) mice and blocking mAb against VCAM-1. Within 8 h, IC challenge of wild-type mice induced edema, hemorrhage, interstitial accumulation of neutrophils and mast cells, as well as production of TNF-alpha and IL-6. All of these inflammatory parameters were reduced significantly in ICAM-1-/- mice. The blockade of VCAM-1 in wild-type mice did not affect any inflammatory parameters. In contrast, ICAM-1-/- mice treated with anti-VCAM-1 mAb had significantly reduced edema, hemorrhage, and neutrophil infiltration. Furthermore, VCAM-1 blockade in ICAM-1-/- mice suppressed cutaneous TNF-alpha and IL-6 production. Thus, VCAM-1 plays a complementary role to ICAM-1 in the cutaneous Arthus reaction by regulating leukocyte accumulation and proinflammatory cytokine production.
Topics: Animals; Arthus Reaction; Edema; Hemorrhage; Intercellular Adhesion Molecule-1; Interleukin-6; Mice; Mice, Inbred C57BL; Mice, Knockout; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Skin; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1
PubMed: 17299025
DOI: 10.1189/jlb.1006623 -
Journal of Anesthesia Apr 2013Neutrophil recruitment to the inflammatory sites is regulated by a variety of adhesion molecules including β2 integrins. The dependency of neutrophil recruitment on β2...
PURPOSE
Neutrophil recruitment to the inflammatory sites is regulated by a variety of adhesion molecules including β2 integrins. The dependency of neutrophil recruitment on β2 integrins is variable in different tissues, but has not yet been verified in the cutaneous passive reverse Arthus reaction. We examined this question and also evaluated the impact of isoflurane on neutrophil recruitment to the skin because we previously showed in vitro that isoflurane binds and inhibits β2 integrins.
METHODS
The dependency on β2 integrins in neutrophil recruitment to the skin in the Arthus reaction was examined using αL, αM and β2 knockout mice. Then, we evaluated the effect of isoflurane on neutrophil recruitment to the skin. In addition, the effects of isoflurane on neutrophil binding to intercellular adhesion molecule-1 (ICAM-1), one of the β2 integrin ligands, were studied in vitro using cell adhesion assays.
RESULTS
Neutrophil recruitment to the skin in the Arthus reaction model was totally dependent on β2 integrins, as β2 knockout mice completely abolished it. However, the defect of only one of the β2 integrins was not sufficient to abolish neutrophil recruitment. Isoflurane reduced neutrophil recruitment to the skin by approximately 90 %. Also, isoflurane inhibited neutrophil adhesion to β2 integrin ligand ICAM-1.
CONCLUSIONS
We demonstrated that (1) neutrophil recruitment to the skin was totally dependent on β2 integrins, and (2) isoflurane significantly impaired neutrophil recruitment. Based on the previous studies on the contribution of other adhesion molecules in neutrophil recruitment, it is likely that isoflurane at least partially affects on β2 integrins in this model.
Topics: Anesthetics, Inhalation; Animals; Arthus Reaction; CD11b Antigen; Cell Adhesion; Flow Cytometry; In Vitro Techniques; Integrin beta Chains; Intercellular Adhesion Molecule-1; Isoflurane; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophil Infiltration; Peroxidase; Skin
PubMed: 23096126
DOI: 10.1007/s00540-012-1508-1 -
The American Journal of Pathology Jun 1988Chlorpromazine blocks antibody-mediated redistribution of cell surface antigens in vitro and in vivo and inhibits the development of passive Heymann glomerulonephritis,...
Chlorpromazine blocks antibody-mediated redistribution of cell surface antigens in vitro and in vivo and inhibits the development of passive Heymann glomerulonephritis, a disease characterized by in situ formation of immune complexes (Camussi et al J Immunol 1986, 136:2127-2135). The aim of this study was to establish whether chlorpromazine exerts similar effects in other rat models characterized by in situ formation of immune complexes. In glomerulonephritis induced by antibodies reactive with an exogenous antigen "planted" in glomeruli pretreatment with chlorpromazine prevented formation of "humps" and exudative and proliferative lesions. Likewise, chlorpromazine prevented passive reverse Arthus reaction in the skin. In contrast, the drug was ineffective when these lesions were already established, and also failed to inhibit the fulminant course of nephrotoxic serum glomerulonephritis with an enhanced autologous phase. It is proposed that the antiinflammatory effect of chlorpromazine is due to its ability to block the recruitment of inflammatory cells and the release of inflammatory mediators.
Topics: Animals; Antigens; Arthus Reaction; Chlorpromazine; Fluorescent Antibody Technique; Glomerulonephritis; Immune Complex Diseases; Kidney Diseases; Kidney Glomerulus; Microscopy, Electron; Renal Artery Obstruction
PubMed: 2968048
DOI: No ID Found -
The Journal of Experimental Medicine Jun 1953The Arthus reaction was studied in guinea pigs passively immunized with human diphtheria antitoxin. Diphtheria toxoid was given intradermally 24 hours following the...
Immunochemical studies of antitoxin produced in normal and allergic individuals hyperimmunized with diphtheria toxoid. III. Studies of the passive Arthus reaction in guinea pigs using human precipitating and nonprecipitating diphtheria antitoxin.
The Arthus reaction was studied in guinea pigs passively immunized with human diphtheria antitoxin. Diphtheria toxoid was given intradermally 24 hours following the intravenous administration of antitoxin and the subsequent reactions were graded and measured. The intensity of Arthus reactions was dependent upon the relative amounts of precipitating antitoxin and toxoid used. Severe lesions were caused by intravenous sensitization with 0.48 mg. precipitating antitoxin N and intradermal challenge with 0.05 or 0.17 toxoid N. Reactions of lesser intensity were caused by smaller amounts of antitoxin and toxoid. The nature of the antibody used for sensitization was of importance in the severity of Arthus reactions. In contrast to the behavior of precipitating antitoxin, amounts of non-precipitating antitoxin equivalent to 0.48 mg. N did not cause severe Arthus reactions when 0.05 or 0.17 mg. toxoid N was given intradermally. Precipitating antitoxic whole serum is altered by heating at 56 degrees C. for 5 hours so that its precipitability is lost without any appreciable loss of antitoxic strength. This modified antitoxin produced Arthus reactions of only intermediate severity in guinea pigs sensitized with 0.48 mg. antitoxin N. When fractions of precipitating antitoxic serum were obtained using a cold ethanol technique described by Deutsch (16), a mixture of the purified gamma(2)-globulin and the crude albumin fraction heated together at 56 degrees C. for 5 hours behaved similarly to whole serum. However, gamma(2)-globulin alone was not affected by the heating procedure, remained precipitable by toxoid, and was able to cause a severe Arthus reaction following sensitization with 0.48 mg. antitoxin N.
Topics: Administration, Intravenous; Animals; Antibodies; Arthus Reaction; Diphtheria; Diphtheria Antitoxin; Diphtheria Toxoid; Guinea Pigs; Humans; Hypersensitivity; Immunization; Vaccination
PubMed: 13069644
DOI: 10.1084/jem.97.6.903 -
Arthritis Research & Therapy Jul 2011The aim was to determine the effect of the Bruton tyrosine kinase (Btk)-selective inhibitor PCI-32765, currently in Phase I/II studies in lymphoma trials, in arthritis...
INTRODUCTION
The aim was to determine the effect of the Bruton tyrosine kinase (Btk)-selective inhibitor PCI-32765, currently in Phase I/II studies in lymphoma trials, in arthritis and immune-complex (IC) based animal models and describe the underlying cellular mechanisms.
METHODS
PCI-32765 was administered in a series of murine IC disease models including collagen-induced arthritis (CIA), collagen antibody-induced arthritis (CAIA), reversed passive anaphylactic reaction (RPA), and passive cutaneous anaphylaxis (PCA). Clinical and pathologic features characteristic of each model were examined following treatment. PCI-32765 was then examined in assays using immune cells relevant to the pathogenesis of arthritis, and where Btk is thought to play a functional role. These included proliferation and calcium mobilization in B cells, cytokine and chemokine production in monocytes/macrophages, degranulation of mast cells and its subsequent cytokine/chemokine production.
RESULTS
PCI-32765 dose-dependently and potently reversed arthritic inflammation in a therapeutic CIA model with an ED(50) of 2.6 mg/kg/day. PCI-32765 also prevented clinical arthritis in CAIA models. In both models, infiltration of monocytes and macrophages into the synovium was completely inhibited and importantly, the bone and cartilage integrity of the joints were preserved. PCI-32765 reduced inflammation in the Arthus and PCA assays. In vitro, PCI-32765 inhibited BCR-activated primary B cell proliferation (IC(50) = 8 nM). Following FcγR stimulation, PCI-32765 inhibited TNFα, IL-1β and IL-6 production in primary monocytes (IC(50) = 2.6, 0.5, 3.9 nM, respectively). Following FcεRI stimulation of cultured human mast cells, PCI-32765 inhibited release of histamine, PGD(2), TNF-α, IL-8 and MCP-1.
CONCLUSIONS
PCI-32765 is efficacious in CIA, and in IC models that do not depend upon autoantibody production from B cells. Thus PCI-32765 targets not only B lymphocytes but also monocytes, macrophages and mast cells, which are important Btk-expressing effector cells in arthritis.
Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; B-Lymphocytes; Cell Proliferation; Female; Humans; Immune Complex Diseases; Macrophages; Mast Cells; Mice; Mice, Inbred BALB C; Monocytes; Piperidines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines
PubMed: 21752263
DOI: 10.1186/ar3400 -
British Journal of Pharmacology Sep 19921. The mechanisms underlying oedema formation induced in a reversed passive Arthus (RPA) reaction and, for comparison, in response to zymosan in rabbit skin were...
1. The mechanisms underlying oedema formation induced in a reversed passive Arthus (RPA) reaction and, for comparison, in response to zymosan in rabbit skin were investigated. 2. Oedema formation at skin sites was quantified by the accumulation of intravenously-injected 125I-labelled human serum albumin. 3. Recombinant soluble complement receptor type 1 (sCR1), administered locally in rabbit skin, suppressed oedema formation induced in the RPA reaction and by zymosan. 4. The platelet-activating factor (PAF) antagonists, WEB 2086 and PF10040 administered locally, inhibited oedema formation induced in the RPA reaction and by PAF but not by zymosan. 5. A locally administered leukotriene B4 (LTB4) antagonist, LY-255283, inhibited oedema formation induced by LTB4 but did not inhibit oedema responses to PAF, zymosan or the RPA reaction. 6. The results demonstrate a role for complement in oedema formation in both the RPA reaction and in response to zymosan. An important contribution by PAF is indicated in the RPA reaction but not in response to zymosan whereas no evidence was obtained to suggest a role for LTB4 in either inflammatory response.
Topics: Animals; Arthus Reaction; Azepines; Complement System Proteins; Edema; Isoquinolines; Leukotriene B4; Platelet Activating Factor; Rabbits; Radioimmunoassay; Receptors, Complement; Tetrazoles; Triazoles; Zymosan
PubMed: 1330163
DOI: 10.1111/j.1476-5381.1992.tb14461.x -
International Journal of Advanced... Mar 2018Platelets regulate inflammation as well as hemostasis. Inflammatory insults often induce hemostatic function through mechanisms that are not always understood. The...
Platelets regulate inflammation as well as hemostasis. Inflammatory insults often induce hemostatic function through mechanisms that are not always understood. The triggering receptor expressed in myeloid cells (TREM)-like transcript 1 (TLT-1) is an abundantly expressed platelet receptor and its deletion leads to hemorrhage and edema after lipopolysaccharide and TNF-α treatment. To define a role for TLT-1 in immune derived bleeding we used a CXCL-2 mediated local inflammatory reaction in the vessels of the cremaster muscle of and wild type mice. Our whole mount immunofluorescent staining of the cremaster muscle demonstrated a 50% reduction in clot size and increased extravasation of plasma molecules in compared to wild type. We demonstrate that the decreased clotting in mice is associated with a 2X reduction in integrin β3 phosphorylation on residue Y773 after platelet activation, which is consistent with mice displaying reduced outside-in signaling and smaller thrombi. We further substantiate TLT-1's role in the regulation of immune derived bleeding using the reverse arthus reaction and demonstrate TLT-1's role in thrombosis using the thromboplastin initiated and collagen/epinephrine models of pulmonary embolism. Thus, the data presented here demonstrate that TLT-1 regulates early clot formation though the stabilization of αIIbβ3 outside-in signaling.
PubMed: 30931337
DOI: 10.21474/IJAR01/7469 -
Canadian Medical Association Journal Dec 1972
Topics: Adult; Allergens; Ampicillin; Animals; Arthus Reaction; Birds; Blood Gas Analysis; Diagnosis, Differential; Feathers; Female; Glucocorticoids; Humans; Hypersensitivity, Immediate; Immunodiffusion; Isoniazid; Lung; Male; Radiography; Respiratory Function Tests; Respiratory Hypersensitivity; Skin Tests; Streptomycin; Tetracycline; Tuberculin Test
PubMed: 4264290
DOI: No ID Found -
Proceedings of the Royal Society of... Apr 1971
Topics: Anaphylaxis; Antigen-Antibody Reactions; Arthus Reaction; Desensitization, Immunologic; Dust; Humans; Hypersensitivity, Delayed; Rhinitis, Allergic, Seasonal; Vaccines
PubMed: 4252736
DOI: No ID Found -
Journal of Bacteriology Feb 1968Defatted human tubercle bacilli, Aoyama B strain, were extracted with 0.1 n NaOH for 24 hr, and the crude polysaccharide fraction was precipitated by the addition of 5...
Defatted human tubercle bacilli, Aoyama B strain, were extracted with 0.1 n NaOH for 24 hr, and the crude polysaccharide fraction was precipitated by the addition of 5 volumes of ethyl alcohol. A yield of 17.8 g of crude polysaccharides was obtained from 800 g of bacilli. The crude polysaccharide was further fractionated into seven fractions by fractional precipitation with ethyl alcohol. Each fraction was purified by successive chromatography on Dowex 50 and diethylaminoethyl cellulose, and by gel filtration on Sephadex G-75 and G-200. Optical rotation and gas chromatographic analyses of purified polysaccharide showed that these polysaccharides contained glucan mannan, arabinomannan, and arabinogalactan. Each polysaccharide was almost completely free from nitrogen, and no tuberculin reaction was produced by 100 mug of each material. Arabinomannan and arabinogalactan showed precipitin reaction, complement fixation, and passive hemagglutination reaction with rabbit antiserum against heat-killed whole bacilli (Aoyama B). In guinea pigs sensitized with Aoyama B bacilli, arabinomannan and arabinogalactan provoked anaphylactic shock when injected intravenously, and Arthus type reaction when injected intracutaneously. With the use of rabbit antiserum, arabinomannan and arabinogalactan showed passive anaphylactic shock, passive cutaneous anaphylaxis, and Prausnitz-Küstner type reactions in guinea pigs. By immunodiffusion analysis, it was shown that the antigenic determinant of arabinomannan was different from that of arabinogalactan.
Topics: Animals; Antigens; Chemical Precipitation; Chemistry Techniques, Analytical; Chromatography; Chromatography, Gas; Chromatography, Gel; Complement Fixation Tests; Guinea Pigs; Hemagglutination Tests; Humans; Hypersensitivity, Immediate; Immunodiffusion; Mycobacterium tuberculosis; Passive Cutaneous Anaphylaxis; Polysaccharides; Polysaccharides, Bacterial; Precipitin Tests
PubMed: 4966538
DOI: 10.1128/jb.95.2.263-271.1968