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Impaired inflammatory responses in the reverse arthus reaction through genetic deletion of the C5a receptor.

Höpken UE, Lu B, Gerard NP, Gerard C - J. Exp. Med. (1997)

Bottom Line: We recently demonstrated that gene-targeted disruption of the C5a anaphylatoxin receptor prevented lung injury in immune complex-mediated inflammation.In this study, we compare the effect of C5aR deficiency in immune complex-induced inflammation in the peritoneal cavity and skin with the results derived from our immune complex alveolitis model.In contrast to our studies in immune complex-induced lung inflammation, C5aR deficiency does not completely prevent injury in the peritoneal cavity and skin.

View Article: PubMed Central - PubMed

Affiliation: Ina Sue Perlmutter Cystic Fibrosis Laboratory, Children's Hospital, Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

ABSTRACT
We recently demonstrated that gene-targeted disruption of the C5a anaphylatoxin receptor prevented lung injury in immune complex-mediated inflammation. In this study, we compare the effect of C5aR deficiency in immune complex-induced inflammation in the peritoneal cavity and skin with the results derived from our immune complex alveolitis model. C5aR- deficient mice exhibit decreased migration of neutrophils and decreased levels of TNF-alpha and interleukin 6 in the peritoneal reverse passive Arthus reaction compared to their wild-type littermates. In the reverse passive Arthus reaction in the skin the C5aR was also required for the full expression of neutrophil influx and edema formation; C5aR-deficient mice showed reduced neutrophil migration and microvascular permeability changes. In contrast to our studies in immune complex-induced lung inflammation, C5aR deficiency does not completely prevent injury in the peritoneal cavity and skin. These data indicate a dominant role for the C5aR and its ligand in the reverse passive Arthus reaction in the lung and a synergistic role together with other inflammatory mediators in immune complex-mediated peritonitis and skin injury.

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Edema formation in the reverse Arthus reaction in the skin. 25 μg of rabbit anti–chicken egg albumin IgG was injected i.d. followed by 20  mg/kg body weight i.v. chicken egg albumin together with 100 μl Evans blue dye (6.25 mg/ml). Dorsal skins were harvested from C5aR (−/−) mice  (striped bars) and their wild-type littermates (black bars) after 3 h and edema was evaluated as weight of 1 cm2 skin sections (A). In addition, edema was quantitated as enhanced microvascular permeability by extraction of extravasated Evan's blue dye with formamide from injected skin sections (B). Ab controls  (Ab control) received Ab to chicken egg albumin intratracheally without i.v. injection of chicken egg albumin. Mice treated with PBS intratracheally followed by i.v. chicken egg albumin served as Ag controls (Ag control). Data are represented as mean ± SEM, n = 8–12 animals in each group. *P <0.001  (A), *P <0.0001 (B).
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Figure 5: Edema formation in the reverse Arthus reaction in the skin. 25 μg of rabbit anti–chicken egg albumin IgG was injected i.d. followed by 20 mg/kg body weight i.v. chicken egg albumin together with 100 μl Evans blue dye (6.25 mg/ml). Dorsal skins were harvested from C5aR (−/−) mice (striped bars) and their wild-type littermates (black bars) after 3 h and edema was evaluated as weight of 1 cm2 skin sections (A). In addition, edema was quantitated as enhanced microvascular permeability by extraction of extravasated Evan's blue dye with formamide from injected skin sections (B). Ab controls (Ab control) received Ab to chicken egg albumin intratracheally without i.v. injection of chicken egg albumin. Mice treated with PBS intratracheally followed by i.v. chicken egg albumin served as Ag controls (Ag control). Data are represented as mean ± SEM, n = 8–12 animals in each group. *P <0.001 (A), *P <0.0001 (B).

Mentions: Edema was measured by determining the wet weight of standardized skin punches at 3 h after treatment. In addition, alterations in vascular permeability were determined by i.v. injection of Evans blue dye 1 h after treatment and quantifying the amount of Evans blue dye in the skin biopsy. Evans blue dye binds to serum proteins and thus can be used to quantify alterations in vascular permeability. The skins of wild-type mice and C5aR-deficient mice were harvested at 3 h after initiation of the Arthus reaction with 25 μg Ab/site. As demonstrated in Fig. 5, A and B, edema was evaluated as weight of skin biopsies (Fig. 5 A) or as Evans blue dye extravasation (Fig. 5 B). No edema was observed in Ag or Ab controls. In both wild-type mice and C5aR-deficient mice profound edema was noticed. However, there was significantly less edema as determined by Evans blue dye extravasation and wet weight of skin biopsies in the C5aR-deficient mice compared to their wild-type littermates (Fig. 5, A and B) 3 h after challenge (permeability changes: 54.7%; weight: 48.1%).


Impaired inflammatory responses in the reverse arthus reaction through genetic deletion of the C5a receptor.

Höpken UE, Lu B, Gerard NP, Gerard C - J. Exp. Med. (1997)

Edema formation in the reverse Arthus reaction in the skin. 25 μg of rabbit anti–chicken egg albumin IgG was injected i.d. followed by 20  mg/kg body weight i.v. chicken egg albumin together with 100 μl Evans blue dye (6.25 mg/ml). Dorsal skins were harvested from C5aR (−/−) mice  (striped bars) and their wild-type littermates (black bars) after 3 h and edema was evaluated as weight of 1 cm2 skin sections (A). In addition, edema was quantitated as enhanced microvascular permeability by extraction of extravasated Evan's blue dye with formamide from injected skin sections (B). Ab controls  (Ab control) received Ab to chicken egg albumin intratracheally without i.v. injection of chicken egg albumin. Mice treated with PBS intratracheally followed by i.v. chicken egg albumin served as Ag controls (Ag control). Data are represented as mean ± SEM, n = 8–12 animals in each group. *P <0.001  (A), *P <0.0001 (B).
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Figure 5: Edema formation in the reverse Arthus reaction in the skin. 25 μg of rabbit anti–chicken egg albumin IgG was injected i.d. followed by 20 mg/kg body weight i.v. chicken egg albumin together with 100 μl Evans blue dye (6.25 mg/ml). Dorsal skins were harvested from C5aR (−/−) mice (striped bars) and their wild-type littermates (black bars) after 3 h and edema was evaluated as weight of 1 cm2 skin sections (A). In addition, edema was quantitated as enhanced microvascular permeability by extraction of extravasated Evan's blue dye with formamide from injected skin sections (B). Ab controls (Ab control) received Ab to chicken egg albumin intratracheally without i.v. injection of chicken egg albumin. Mice treated with PBS intratracheally followed by i.v. chicken egg albumin served as Ag controls (Ag control). Data are represented as mean ± SEM, n = 8–12 animals in each group. *P <0.001 (A), *P <0.0001 (B).
Mentions: Edema was measured by determining the wet weight of standardized skin punches at 3 h after treatment. In addition, alterations in vascular permeability were determined by i.v. injection of Evans blue dye 1 h after treatment and quantifying the amount of Evans blue dye in the skin biopsy. Evans blue dye binds to serum proteins and thus can be used to quantify alterations in vascular permeability. The skins of wild-type mice and C5aR-deficient mice were harvested at 3 h after initiation of the Arthus reaction with 25 μg Ab/site. As demonstrated in Fig. 5, A and B, edema was evaluated as weight of skin biopsies (Fig. 5 A) or as Evans blue dye extravasation (Fig. 5 B). No edema was observed in Ag or Ab controls. In both wild-type mice and C5aR-deficient mice profound edema was noticed. However, there was significantly less edema as determined by Evans blue dye extravasation and wet weight of skin biopsies in the C5aR-deficient mice compared to their wild-type littermates (Fig. 5, A and B) 3 h after challenge (permeability changes: 54.7%; weight: 48.1%).

Bottom Line: We recently demonstrated that gene-targeted disruption of the C5a anaphylatoxin receptor prevented lung injury in immune complex-mediated inflammation.In this study, we compare the effect of C5aR deficiency in immune complex-induced inflammation in the peritoneal cavity and skin with the results derived from our immune complex alveolitis model.In contrast to our studies in immune complex-induced lung inflammation, C5aR deficiency does not completely prevent injury in the peritoneal cavity and skin.

View Article: PubMed Central - PubMed

Affiliation: Ina Sue Perlmutter Cystic Fibrosis Laboratory, Children's Hospital, Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

ABSTRACT
We recently demonstrated that gene-targeted disruption of the C5a anaphylatoxin receptor prevented lung injury in immune complex-mediated inflammation. In this study, we compare the effect of C5aR deficiency in immune complex-induced inflammation in the peritoneal cavity and skin with the results derived from our immune complex alveolitis model. C5aR- deficient mice exhibit decreased migration of neutrophils and decreased levels of TNF-alpha and interleukin 6 in the peritoneal reverse passive Arthus reaction compared to their wild-type littermates. In the reverse passive Arthus reaction in the skin the C5aR was also required for the full expression of neutrophil influx and edema formation; C5aR-deficient mice showed reduced neutrophil migration and microvascular permeability changes. In contrast to our studies in immune complex-induced lung inflammation, C5aR deficiency does not completely prevent injury in the peritoneal cavity and skin. These data indicate a dominant role for the C5aR and its ligand in the reverse passive Arthus reaction in the lung and a synergistic role together with other inflammatory mediators in immune complex-mediated peritonitis and skin injury.

Show MeSH
Related in: MedlinePlus