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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: 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 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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Role of C5a in neutrophil elicitation in immune complex–induced peritonitis. The reverse passive Arthus reaction was allowed to proceed  for 4 h (A) or 8 h (B) in C5aR (−/−) mice (striped bars) and their wild-type littermates (black bars). Total cell numbers (data not shown) and percentage  of neutrophils in the peritoneal fluid were determined as described previously (13). Ab controls (Ab control) received Ab to chicken egg albumin i.p. without i.v. injection of chicken egg albumin. Mice treated with PBS i.p. followed by i.v. chicken egg albumin served as Ag controls (Ag control). Data are  represented as mean ± SEM, n = 7–8 mice *P <0.004 (A), and n = 8–11 mice *P <0.05 (B).
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Figure 1: Role of C5a in neutrophil elicitation in immune complex–induced peritonitis. The reverse passive Arthus reaction was allowed to proceed for 4 h (A) or 8 h (B) in C5aR (−/−) mice (striped bars) and their wild-type littermates (black bars). Total cell numbers (data not shown) and percentage of neutrophils in the peritoneal fluid were determined as described previously (13). Ab controls (Ab control) received Ab to chicken egg albumin i.p. without i.v. injection of chicken egg albumin. Mice treated with PBS i.p. followed by i.v. chicken egg albumin served as Ag controls (Ag control). Data are represented as mean ± SEM, n = 7–8 mice *P <0.004 (A), and n = 8–11 mice *P <0.05 (B).

Mentions: Previously we demonstrated the critical role for complement in immune complex– mediated acute lung injury (21) by challenging the C5aR (−/−) mice, selectively eliminating contributions of the C5a anaphylatoxin. In this study we investigated the role of the C5a receptor in the recruitment and activation of acute inflammatory leukocytes in the peritoneal reverse passive Arthus reaction. Administration of rabbit anti–chicken egg albumin Ab in the peritoneal cavity after i.v. injection of chicken egg albumin caused neutrophil influx into the peritoneal cavity as well as secretion of diverse inflammatory cytokines. C5aR-deficient mice showed significantly reduced neutrophil migration compared to their wild-type controls at 4 h (Fig. 1 A) and at 8 h (Fig. 1 B) of the reverse passive Arthus reaction. Neutrophil accumulation reached a maximum at 8 h in both sets of mice. However, the decrease in leukocyte influx in C5aR (−/−) mice compared to their wild-type controls was more profound at 4 h (74%) than at 8 h (51%) suggesting that C5a might contribute more to the initiation of the Arthus reaction rather than in the subsequent recruitment and activation steps.


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)

Role of C5a in neutrophil elicitation in immune complex–induced peritonitis. The reverse passive Arthus reaction was allowed to proceed  for 4 h (A) or 8 h (B) in C5aR (−/−) mice (striped bars) and their wild-type littermates (black bars). Total cell numbers (data not shown) and percentage  of neutrophils in the peritoneal fluid were determined as described previously (13). Ab controls (Ab control) received Ab to chicken egg albumin i.p. without i.v. injection of chicken egg albumin. Mice treated with PBS i.p. followed by i.v. chicken egg albumin served as Ag controls (Ag control). Data are  represented as mean ± SEM, n = 7–8 mice *P <0.004 (A), and n = 8–11 mice *P <0.05 (B).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2199021&req=5

Figure 1: Role of C5a in neutrophil elicitation in immune complex–induced peritonitis. The reverse passive Arthus reaction was allowed to proceed for 4 h (A) or 8 h (B) in C5aR (−/−) mice (striped bars) and their wild-type littermates (black bars). Total cell numbers (data not shown) and percentage of neutrophils in the peritoneal fluid were determined as described previously (13). Ab controls (Ab control) received Ab to chicken egg albumin i.p. without i.v. injection of chicken egg albumin. Mice treated with PBS i.p. followed by i.v. chicken egg albumin served as Ag controls (Ag control). Data are represented as mean ± SEM, n = 7–8 mice *P <0.004 (A), and n = 8–11 mice *P <0.05 (B).
Mentions: Previously we demonstrated the critical role for complement in immune complex– mediated acute lung injury (21) by challenging the C5aR (−/−) mice, selectively eliminating contributions of the C5a anaphylatoxin. In this study we investigated the role of the C5a receptor in the recruitment and activation of acute inflammatory leukocytes in the peritoneal reverse passive Arthus reaction. Administration of rabbit anti–chicken egg albumin Ab in the peritoneal cavity after i.v. injection of chicken egg albumin caused neutrophil influx into the peritoneal cavity as well as secretion of diverse inflammatory cytokines. C5aR-deficient mice showed significantly reduced neutrophil migration compared to their wild-type controls at 4 h (Fig. 1 A) and at 8 h (Fig. 1 B) of the reverse passive Arthus reaction. Neutrophil accumulation reached a maximum at 8 h in both sets of mice. However, the decrease in leukocyte influx in C5aR (−/−) mice compared to their wild-type controls was more profound at 4 h (74%) than at 8 h (51%) suggesting that C5a might contribute more to the initiation of the Arthus reaction rather than in the subsequent recruitment and activation steps.

Bottom Line: 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 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