C5a, cutaneous mast cells, and inflammation: In vitro and in vivo studies in a murine model

Henry W. Lim, Dan He, Susana Esquenazi-Behar, Kim B. Yancey, Nicholas A. Soter

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Abstract

To evaluate further the interactions of C5a and mast cells in cutaneous inflammation, the ability of human native C5a (nC5a) (10 to 500 ng/ml) and human recombinant C5a (rC5a) (10 ng/ml to 100 ng/ml) to induce histamine release from purified BALB/c cutaneous mast cells (CMC) and peritoneal mast cells (PMC) was analyzed. It was found that nC5a induced histamine release from CMC but not from PMC, with a maximal net release at 250 ng/ml nC5a (22.8 ± 2.6%). Kinetic experiments demonstrated that nC5a-induced maximal net histamine release occurred 5 min after the presentation of this stimulus (25.8 ± 6.0%). Using rC5a and CMC, dose-response studies indicated a maximal net release of 7.0 ± 1.7% at rC5a of 10 ng/ml, and kinetic studies showed a maximal net release at 5 min of incubation (12.9 ± 1.6%). Release induced by rC5a was calcium-dependent, and peaked at 30°C. These results indicate that functional heterogeneity exists between the CMC and the PMC of BALB/c mice, that C5a is a relevant stimulus for characterization of this heterogeneity, and that CMC from these animals can serve as a convenient in vitro model for the study of human C5a-mast cell interactions. In vivo, injections of nC5a (25-100 ng) and rC5a (25-100 ng) into the skin of BALB/c mice induced an increase in cutaneous vasopermeability, as assessed by the extravasation of intravenously injected 125I-bovine serum albumin. nC5a induced a dose-dependent increase in vasopermeability, whereas alterations induced by rC5a plateaued at 50 ng. The C5a-induced vasopermeability was markedly enhanced in animals that had been previously treated with an inhibitor of serum carboxypeptidase, which converts C5a to the less potent derivative, C5a des Arg. These findings suggest that carboxypeptidase plays an important role in vivo in the modulation of C5a-induced cutaneous inflammation in murine skin.

Original languageEnglish (US)
Pages (from-to)305-311
Number of pages7
JournalJournal of Investigative Dermatology
Volume97
Issue number2
StatePublished - Aug 1991

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Mast Cells
Histamine
Carboxypeptidases
Inflammation
Skin
Animals
Kinetics
Bovine Serum Albumin
Histamine Release
Modulation
Calcium
Derivatives
In Vitro Techniques
Experiments
Cell Communication
Injections
Serum

ASJC Scopus subject areas

  • Dermatology

Cite this

C5a, cutaneous mast cells, and inflammation : In vitro and in vivo studies in a murine model. / Lim, Henry W.; He, Dan; Esquenazi-Behar, Susana; Yancey, Kim B.; Soter, Nicholas A.

In: Journal of Investigative Dermatology, Vol. 97, No. 2, 08.1991, p. 305-311.

Research output: Contribution to journalArticle

Lim, Henry W. ; He, Dan ; Esquenazi-Behar, Susana ; Yancey, Kim B. ; Soter, Nicholas A. / C5a, cutaneous mast cells, and inflammation : In vitro and in vivo studies in a murine model. In: Journal of Investigative Dermatology. 1991 ; Vol. 97, No. 2. pp. 305-311.
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abstract = "To evaluate further the interactions of C5a and mast cells in cutaneous inflammation, the ability of human native C5a (nC5a) (10 to 500 ng/ml) and human recombinant C5a (rC5a) (10 ng/ml to 100 ng/ml) to induce histamine release from purified BALB/c cutaneous mast cells (CMC) and peritoneal mast cells (PMC) was analyzed. It was found that nC5a induced histamine release from CMC but not from PMC, with a maximal net release at 250 ng/ml nC5a (22.8 ± 2.6{\%}). Kinetic experiments demonstrated that nC5a-induced maximal net histamine release occurred 5 min after the presentation of this stimulus (25.8 ± 6.0{\%}). Using rC5a and CMC, dose-response studies indicated a maximal net release of 7.0 ± 1.7{\%} at rC5a of 10 ng/ml, and kinetic studies showed a maximal net release at 5 min of incubation (12.9 ± 1.6{\%}). Release induced by rC5a was calcium-dependent, and peaked at 30°C. These results indicate that functional heterogeneity exists between the CMC and the PMC of BALB/c mice, that C5a is a relevant stimulus for characterization of this heterogeneity, and that CMC from these animals can serve as a convenient in vitro model for the study of human C5a-mast cell interactions. In vivo, injections of nC5a (25-100 ng) and rC5a (25-100 ng) into the skin of BALB/c mice induced an increase in cutaneous vasopermeability, as assessed by the extravasation of intravenously injected 125I-bovine serum albumin. nC5a induced a dose-dependent increase in vasopermeability, whereas alterations induced by rC5a plateaued at 50 ng. The C5a-induced vasopermeability was markedly enhanced in animals that had been previously treated with an inhibitor of serum carboxypeptidase, which converts C5a to the less potent derivative, C5a des Arg. These findings suggest that carboxypeptidase plays an important role in vivo in the modulation of C5a-induced cutaneous inflammation in murine skin.",
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N2 - To evaluate further the interactions of C5a and mast cells in cutaneous inflammation, the ability of human native C5a (nC5a) (10 to 500 ng/ml) and human recombinant C5a (rC5a) (10 ng/ml to 100 ng/ml) to induce histamine release from purified BALB/c cutaneous mast cells (CMC) and peritoneal mast cells (PMC) was analyzed. It was found that nC5a induced histamine release from CMC but not from PMC, with a maximal net release at 250 ng/ml nC5a (22.8 ± 2.6%). Kinetic experiments demonstrated that nC5a-induced maximal net histamine release occurred 5 min after the presentation of this stimulus (25.8 ± 6.0%). Using rC5a and CMC, dose-response studies indicated a maximal net release of 7.0 ± 1.7% at rC5a of 10 ng/ml, and kinetic studies showed a maximal net release at 5 min of incubation (12.9 ± 1.6%). Release induced by rC5a was calcium-dependent, and peaked at 30°C. These results indicate that functional heterogeneity exists between the CMC and the PMC of BALB/c mice, that C5a is a relevant stimulus for characterization of this heterogeneity, and that CMC from these animals can serve as a convenient in vitro model for the study of human C5a-mast cell interactions. In vivo, injections of nC5a (25-100 ng) and rC5a (25-100 ng) into the skin of BALB/c mice induced an increase in cutaneous vasopermeability, as assessed by the extravasation of intravenously injected 125I-bovine serum albumin. nC5a induced a dose-dependent increase in vasopermeability, whereas alterations induced by rC5a plateaued at 50 ng. The C5a-induced vasopermeability was markedly enhanced in animals that had been previously treated with an inhibitor of serum carboxypeptidase, which converts C5a to the less potent derivative, C5a des Arg. These findings suggest that carboxypeptidase plays an important role in vivo in the modulation of C5a-induced cutaneous inflammation in murine skin.

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