The Role of Complement-Derived Chemotactic Factors in Lung Injury Induced by Preformed Immune Complexes

Tanoue, Masahiko; Yoshizawa, Yasuyuki; Sato, Tetsuo; Yano, Heiichi; Kimula, Yuji; Miyamoto, Kiyomi

doi:10.1159/000236497

Cited by 5 publications

(4 citation statements)

References 10 publications

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“…It is well established that certain complement factors promote chemotaxis of neutrophils towards the site of inflammation. In accordance with our study, CVF treatment was reported to reduce accumulation of neutrophils in the site of lung injury [35]. The delayed onset of leucocytosis consistent with a chemotactic role of complement in normal animals was likewise observed in decomplemented rabbits in the model of pneumococcal meningitis [36].…”

Section: Discussionsupporting

confidence: 89%

Complement depletion aggravatesStaphylococcus aureussepticaemia and septic arthritis

Sakiniene

Bremell

Tarkowski

1999

Clinical and Experimental Immunology

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SUMMARYThe aim of the study was to assess the role of the complement system in Staphylococcus aureus arthritis and septicaemia. The murine model of haematogenously acquired septic arthritis was used, injecting intravenously toxic shock syndrome toxin-1 (TSST-1), producing S. aureus LS-1. Complement was depleted using cobra venom factor (CVF). Evaluation of arthritis was performed clinically and histopathologically. In addition, the effect of complement depletion on the phagocytic activity of leucocytes was assessed in vivo and in vitro. Six days after inoculation of S. aureus the prevalence of arthritis in decomplemented mice was three-fold higher than that in controls (91% versus 25%). The clinical severity of arthritis at the end of the experiment, expressed as arthritic index, was 7·3 and 1·9, respectively. These findings were confirmed by histological index of synovitis as well as of cartilage and/or bone destruction being significantly higher in decomplemented mice than in controls (9·8 Ϯ 1·7 versus 4·9 Ϯ 1·2, P < 0·05; and 7·9 Ϯ 1·7 versus 3·0 Ϯ 0·9, P < 0·05, respectively). Also, the septicaemiainduced mortality was clearly higher in decomplemented mice compared with the controls. CVF treatment significantly reduced in vivo polymorphonuclear cell-dependent inflammation induced by subcutaneous injection of olive oil and mirroring the capacity of polymorphonuclear cells (PMNC) to migrate and/or extravasate. Besides, the decomplementation procedure significantly impaired phagocytic activity of peripheral blood leucocytes in vitro, since the number of phagocytes being able to ingest bacteria decreased by 50% when the cells were maintained in decomplemented serum compared with those in intact serum. The conclusion is that complement depletion aggravates the clinical course of S. aureus arthritis and septicaemia, possibly by a combination of decreased migration/extravasation of PMNC and an impairment of phagocytosis.

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Section: Discussionsupporting

confidence: 89%

Complement depletion aggravatesStaphylococcus aureussepticaemia and septic arthritis

Sakiniene

Bremell

Tarkowski

1999

Clinical and Experimental Immunology

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“…When no granulomas are formed, more antigen might escape the lung and be available for formation of circulating immune complexes. Previous studies have suggested that immune complexes increase lung permeability (32).…”

Section: Discussionmentioning

confidence: 99%

Interferon-gamma is necessary for the expression of hypersensitivity pneumonitis.

Guðmundsson¹,

Hunninghake²

1997

J. Clin. Invest.

148

132

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Farmers lung disease is a common form of hypersensitivity pneumonitis (HP) and is characterized by inflammation and granuloma formation in the lung. Interferon-␥ is important for the expression of granulomatous diseases caused by infectious agents; however, the role this mediator in regulating expression of the granulomatous response to inhaled antigen is not known. To evaluate this, we compared the response to inhaled antigen of mice that do not express the gene coding for interferon-␥ (GKO) with that of their normal littermates (WT). GKO and WT mice on a BALB/c background were exposed to 150 g of the thermophilic bacteria Saccharopolyspora rectivirgula or saline alone, for three consecutive days a week, for 3 wk. After exposure to antigen, WT mice developed a marked granulomatous inflammation associated with an increase in lung weight and numbers of cells in bronchoalveolar lavage fluid (BAL). Although GKO mice also exhibited an increase in lung weight and numbers of cells in BAL fluid, they developed minimal inflammation and no granulomas after a similar exposure to antigen. To further evaluate if the lack of a response to antigen in GKO mice was due to lack of IFN -␥ , we replaced this mediator via intraperitoneal injections. When given replacement IFN-␥ , the GKO mice developed granulomatous inflammation in the lung. These studies show that IFN-␥ is essential for the expression of hypersensitivity pneumonitis. ( J. Clin. Invest. 1997. 99:2386-2390.)

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“…In previous studies we have suggested that CD11b + leucocyte infiltration is a result of complement activation [5,8]. The anaphylatoxins C3a and C5a, released upon activation, are known to be major mediators for neutrophilic granulocyte migration [28]. In a follow‐up study in which melagatran, a direct thrombin inhibitor, was used to inhibit the IBMIR, both coagulation and complement were abrogated.…”

Section: Discussionmentioning

confidence: 99%

Neutrophilic granulocytes are the predominant cell type infiltrating pancreatic islets in contact with ABO-compatible blood

Moberg

Korsgren

Nilsson

2005

Clinical and Experimental Immunology

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SummaryThe poor outcome of intraportal islet transplantation may be explained by the instant blood-mediated inflammatory reaction (IBMIR), characterized by islet entrapment in blood clots, leucocyte infiltration and disruption of islet morphology. Here we employ a newly developed in vitro system to identify the blood cells involved in this process. Islets were mixed with ABO-compatible blood in heparinized tubes and incubated for various times up to 6 h. Clots were analysed immunohistochemically for detection of platelets (CD41a), leucocytes/lymphocytes (CD11b), granulocytes (CD16, lysozyme), neutrophilic granulocytes (neutrophil elastase), eosinophilic granulocytes (NaCN + + + + H 2 O 2 ), macrophages (CD68), dendritic cells (CD209/DC-SIGN), B cells (CD20) and T cells (CD4, CD8). Platelets were rapidly deposited around the islets in contact with the blood, reaching a maximum by 30 min. The first neutrophilic granulocytes appeared in the islets after 15 min, increased at 1 h and peaked at 2 h. Small numbers of macrophages were found infiltrating the islets already after 5 min, with a slight increase over time. However, control stainings of cultured islets and pancreas biopsies identified these cells as being largely of donor origin. No T cells, B cells, dendritic cells or eosinophilic granulocytes were detected during the 6 h observation time. Neutrophilic granulocytes were identified as the main infiltrating blood cell in islets exposed to blood, implying that these cells play a key role in clinical islet transplantation. Because islets are known to be exquisitely susceptible to oxidative stress, development of drugs targeting neutrophilic cytotoxicity could markedly improve the outcome of islet transplantation.

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The Role of Complement-Derived Chemotactic Factors in Lung Injury Induced by Preformed Immune Complexes

Cited by 5 publications

References 10 publications

Complement depletion aggravatesStaphylococcus aureussepticaemia and septic arthritis

Complement depletion aggravatesStaphylococcus aureussepticaemia and septic arthritis

Interferon-gamma is necessary for the expression of hypersensitivity pneumonitis.

Neutrophilic granulocytes are the predominant cell type infiltrating pancreatic islets in contact with ABO-compatible blood

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