Evidence for antibody-catalyzed ozone formation in bacterial killing and inflammation.
(17/146)
Recently, we showed that antibodies catalyze the generation of hydrogen peroxide (H2O2) from singlet molecular oxygen (1O2*) and water. Here, we show that this process can lead to efficient killing of bacteria, regardless of the antigen specificity of the antibody. H2O2 production by antibodies alone was found to be not sufficient for bacterial killing. Our studies suggested that the antibody-catalyzed water-oxidation pathway produced an additional molecular species with a chemical signature similar to that of ozone. This species is also generated during the oxidative burst of activated human neutrophils and during inflammation. These observations suggest that alternative pathways may exist for biological killing of bacteria that are mediated by potent oxidants previously unknown to biology. (+info)
The role of humoral immunity and acute inflammation in protection against staphyloccocal dermonecrosis.
(18/146)
Mice were protected against the dermonecrotic effects of Staphylococcus aureus by previous infection with either coagulase-positive or coagulase-negative strains or by immunization with alpha-toxin. Passive protection was conferred by serum from previously infected mice or by alpha-antitoxin. While only some of these methods were associated with circulating alpha-antitoxin, in all cases there was a brisk early inflammatory response to infection. Furthermore, if the capacity of well immunized mice to mount such a response was removed, they were no longer protected against dermonecrosis. Conversely, non-immune mice developed little or no necrosis if the staphylococci were injected into areas of preexisting non-specific acute inflammation whether these had been produced chemically or immunologically. It is suggested that in this model of local infection with S. aureus an early inflammatory response, however provoked, is the major protective factor. Though specific neutralizing actions of antibodies are not excluded, the most important result of antibody-antigen reaction is to cause local inflammation by some form of immediate hyersensitivity. (+info)
Fc receptor-independent development of autoimmune glomerulonephritis in lupus-prone MRL/lpr mice.
(19/146)
OBJECTIVE: To determine the role of Fc receptors (FcR), which play crucial roles in antibody and immune complex-mediated inflammation and autoimmunity, including glomerulonephritis (GN), in the development of autoimmune GN and vasculitis in MRL/lpr mice, one of the most widely used lupus-prone mouse models. METHODS: FcRgamma(-/-) MRL/lpr mice were generated by backcrossing for 8 generations. The development of GN and vasculitis of various sized vessels was analyzed histopathologically in the kidney, lung, and skin. Autoantibody and immune complex levels were determined biochemically at 16-24 weeks of age and compared with the findings in FcRgamma(+) MRL/lpr mice. The lifespan of the mice was also recorded. RESULTS: Diffuse proliferative GN, with deposition of IgG and C3, developed in both FcRgamma(-/-) and FcRgamma(+) MRL/lpr mice. There was no difference in the survival rate and degree of proteinuria between FcRgamma(+) and FcRgamma(-/-) MRL/lpr mice. Regardless of the level of FcR expression, there were no significant differences in the levels of serum IgG, anti-DNA antibody, or circulating immune complexes between the two types of mice. Necrotizing vasculitis in medium-sized arteries of the kidneys and lungs as well as small-vessel vasculitis in the skin was observed in both in FcRgamma(+) and FcRgamma(-/-) MRL/lpr mice. In contrast, the Arthus reaction was induced in FcRgamma(+) MRL/lpr mice, but not in FcRgamma(-/-) MRL/lpr mice. CONCLUSION: Unlike (NZB x NZW)F(1), the other strain of lupus-prone mice that develops GN in an FcR-dependent manner, the development of autoimmune GN and vasculitis in MRL/lpr mice was FcR-independent, implying heterogeneity of the contribution of FcR to the development of autoimmune disease. (+info)
A peptide derived from the parasite receptor, complement C2 receptor inhibitor trispanning, suppresses immune complex-mediated inflammation in mice.
(20/146)
Complement C2 receptor inhibitor trispanning (CRIT) is a Schistosoma protein that binds the human complement protein, C2. We recently showed that peptides based on the ligand binding region of CRIT inhibit the classical pathway (CP) of complement activation in human serum, using hemolytic assays and so speculated that on the parasite surface CRIT has the function of evading human complement. We now show that in vitro the C2-binding 11-aa C terminus of the first extracellular domain of CRIT, a 1.3-kDa peptide termed CRIT-H17, inhibits CP activation in a species-specific manner, inhibiting mouse and rat complement but not that from guinea pig. Hitherto, the ability of CRIT to regulate complement in vivo has not been assessed. In this study we show that by inhibiting the CP, CRIT-H17 is able to reduce immune complex-mediated inflammation (dermal reversed passive Arthus reaction) in BALB/c mice. Upon intradermal injection of CRIT-H17, and similarly with recombinant soluble complement receptor type 1, there was a 41% reduction in edema and hemorrhage, a 72% reduction in neutrophil influx, and a reduced C3 deposition. Furthermore, when H17 was administered i.v. at a 1 mg/kg dose, inflammation was reduced by 31%. We propose that CRIT-H17 is a potential therapeutic agent against CP complement-mediated inflammatory tissue destruction. (+info)
Relative contributions of selectins and intercellular adhesion molecule-1 to tissue injury induced by immune complex deposition.
(21/146)
Immune complex-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the relative contribution of adhesion molecules, including selectins and ICAM-1, in this pathogenetic process, the cutaneous passive Arthus reaction was examined in mice lacking E-selectin, P-selectin, or both L-selectin and ICAM-1 with anti-P- or E-selectin mAbs. Edema and hemorrhage were significantly reduced in P-selectin(-/-) mice compared with wild-type mice while they were not inhibited in E-selectin(-/-) mice. Combined E- and P-selectin blockade resulted in more significant reduction relative to L-selectin/ICAM-1(-/-) as well as P-selectin(-/-) mice. Remarkably, both E- and P-selectin blockade in L-selectin/ICAM-1(-/-) mice completely abrogated edema and hemorrhage. The inhibited edema and hemorrhage paralleled reduced infiltration of neutrophils and mast cells that expressed significant levels of P-selectin glycoprotein ligand-1. Similarly reduced infiltration of neutrophils and mast cells was observed in the peritoneal Arthus reaction and was associated partly with the decreased production of tumor necrosis factor-alpha and interleukin-6. The results of this study indicate that both endothelial selectins contribute predominantly to the Arthus reaction by regulating mast cell and neutrophil infiltration and that the full development of the Arthus reaction is mediated cooperatively by all selectins and ICAM-1. (+info)
Mechanism of trapping of immune complexes in joint collagenous tissues.
(22/146)
The role of acute inflammation and of pre-existing specific antibody in the retention of intra-articular antigen in joint collagenous tissues of immunized rabbits was examined. The role of the acute synovitis occurring immediately after antigen injection was investigated by the production of acute synovitis in immune and non-immune rabbits. In no case was more 125I-labelled BSA retained in the inflamed joint tissues compared to the contralateral non-inflamed joints 7 days after intrarticular antigen injection. When antigen retention was examined early after intra-articular injection, the largest amount of antigen was retained 30 min after injection, before the appearance of the acute inflammatory synovitis. These findings suggest that acute inflammation does not constitute a major factor in the long-term retention of antigen in collagenous tissues. To investigate the role of antibody in the retention of antigen, non-immune rabbits were injected intravenously with purified anti-BSA antibody 3 days prior to the intra-articular injection of BSA. Over 20 times more antigen was retained irreversibly in collagenous tissues obtained from the injected joints of passively immunized animals compared with similar tissues of control rabbits. When rabbits were injected intravenously with purified anti-BSA antibody and either killed 20 mins or 3 days later, in vitro binding of antigen by joint collagenous tissues was seen only in animals where antibody was allowed to equilibrate with the extravascular space for 3 days. These findings indicate that retention of antigen depends on the presence of extravascular antibody. Antigen retention in collagenous tissues was also present when both antibody and antigen were injected intravenously and antibody was given 3 days before the antigen. It is concluded that the trapping of immune complexes in collagenous joint tissues of immunized animals depends on: the presence of antibody in the extra-vascular space; the diffusion of antigen or soluble complexes into this space; the interaction of antigen or soluble complexes with extravascular antibody with subsequent formation of larger and more insoluble complexes; and the trapping of these complexes within the collagen fibre meshwork. (+info)
Studies on delayed hypersensitivity pleural exudates in guinea pigs. I. Demonstration of substances in the cell-free exudate which cause inhibition of mononuclear cell migration in vitro.
(23/146)
Leucocyte migration inhibitory (MI) activity was investigated in vitro in the delayed hypersensitivity reaction induced by intrapleural injection of PPD into FCA-sensitized guinea-pigs. During the initial reaction (6 h) two types of antigen-dependent MI activity were detected in serum and cell-free exudate. One was of high molecular weight and associated with immunoglobulin and the other was of low molecular weight and appeared to be related to so-called "antigen-dependent MIF". As the reaction progressed (i.e. 12-24 h), two types of antigen-dependent MI activity were revealed in exudate, but not in serum. One was high molecular weight and the other was low molecular weight and thought to be related to so-called "antigen-independent MIF". Similar experiments were performed on the reverse passive Arthus reaction in the pleural cavity of guinea-pigs. A high molecular weight MI activity was detected in 6-h cell-free exudate and was found to be antigen-independent. "So-called MIF" was not found in this reaction. (+info)
Studies on delayed hypersensitivity pleural exudates in guinea-pigs. II. The interrelationship of monocytic and lymphocytic cells with respect to migration activity.
(24/146)
The in vitro migration activity of monocytic cells and the effect of lymphocytes in the delayed hypersensitivity (DH) reaction induced by intrapleural injection of PPD into FCA-sensitized guinea-pigs was investigated. The in vitro migration of exudate mononuclear cells was lower than that of comparable blood cells, and continued to decrease as the reaction progressed. An inverse relaationship was observed between the migration area and cell volume of mononuclear cells from both blood and exudate. Similar experiments were performed on the reversed passive Arthus (RPA) reaction in the pleural cavity of guinea-pigs. For 6-h exudate, the mononuclear cell migration exceeded that for blood mononuclear cells. However, the migration of mononuclear cells from 18-h exudates was markedly reduced. As with DH, an inverse relationship between the migration area and cell volume was observed with the mononuclear cells of RPA exudates. Following the addition of antigen, the migration of DH exudate mononuclear cells was inhibited whereas the exudate mononuclear cells of the RPA reaction remained unaffected. For DH, the inhibition of migration induced by antigen appeared to be related to the non-adherent cells of 6-h exudates, and both the adherent and non-adherent cells of 18-h exudates. (+info)