Limits...
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.

Show MeSH

Related in: MedlinePlus

PMN infiltration in the reverse Arthus reaction in the skin.  Extraction of MPO from skin of C5aR (−/−) (striped bars) mice and their  wild-type littermates (black bars) was performed 8 h after initiation of the  Arthus reaction. 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 = 12–13 animals in each group. *P <0.003.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2199021&req=5

Figure 4: PMN infiltration in the reverse Arthus reaction in the skin. Extraction of MPO from skin of C5aR (−/−) (striped bars) mice and their wild-type littermates (black bars) was performed 8 h after initiation of the Arthus reaction. 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 = 12–13 animals in each group. *P <0.003.

Mentions: Leukocyte influx in the reverse Arthus reaction in the skin reaches a maximum at 8 h after challenge (25). Therefore, we evaluated neutrophil influx at 8 h. The margination of neutrophils was quantitated by using the myeloid specific enzyme MPO as an indicator of neutrophil accumulation. With a dose of 100 μg Ab/site, a dramatic PMN influx was observed at 8 h. As demonstrated in Fig. 4 the MPO activity in C5aR-deficient mice was significantly lower (43.8%) than in wild-type littermates. No MPO activity was detected in skin which was treated only with PBS and only very weak MPO activity was observed when mice were treated with 100 μg Ab/site without application of Ag.


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)

PMN infiltration in the reverse Arthus reaction in the skin.  Extraction of MPO from skin of C5aR (−/−) (striped bars) mice and their  wild-type littermates (black bars) was performed 8 h after initiation of the  Arthus reaction. 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 = 12–13 animals in each group. *P <0.003.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199021&req=5

Figure 4: PMN infiltration in the reverse Arthus reaction in the skin. Extraction of MPO from skin of C5aR (−/−) (striped bars) mice and their wild-type littermates (black bars) was performed 8 h after initiation of the Arthus reaction. 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 = 12–13 animals in each group. *P <0.003.
Mentions: Leukocyte influx in the reverse Arthus reaction in the skin reaches a maximum at 8 h after challenge (25). Therefore, we evaluated neutrophil influx at 8 h. The margination of neutrophils was quantitated by using the myeloid specific enzyme MPO as an indicator of neutrophil accumulation. With a dose of 100 μg Ab/site, a dramatic PMN influx was observed at 8 h. As demonstrated in Fig. 4 the MPO activity in C5aR-deficient mice was significantly lower (43.8%) than in wild-type littermates. No MPO activity was detected in skin which was treated only with PBS and only very weak MPO activity was observed when mice were treated with 100 μg Ab/site without application of Ag.

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