Role of resident peritoneal macrophages and mast cells in chemokine production and neutrophil migration in acute inflammation

Evidence for an inhibitory loop involving endogenous IL-10

Maureen N. Ajuebor, Anuk M. Das, L. Virag, Roderick J. Flower, Csaba Szabó, Mauro Perretti

Research output: Contribution to journalArticle

240 Citations (Scopus)

Abstract

The roles played by resident macrophages (Mφ) and mast cells (MCs) in polymorphonuclear leukocyte (PMN) accumulation and chemokine production within the mouse peritoneal cavity in response to administration of zymosan (0.2 and 1 mg), LPS (1 mg/kg), and thioglycolate (0.5 ml of a 3% suspension) were investigated. A marked reduction (>95%) in intact MC numbers was obtained by pretreatment with the MC activator compound 48/80, whereas resident Mφ were greatly diminished (>85%) by a 3-day treatment with liposomes encapsulating the cytotoxic drug dichloromethylene-bisphosphonate. No modulation of thioglycolate-induced inflammation was seen with either pretreatment. Removal of either MCs or Mφ attenuated LPS-induced PMN extravasation without affecting the levels of the chemokines murine monocyte chemoattractant protein-1 and KC measured in the lavage fluids. In contrast, MC depletion inhibited PMN accumulation and murine monocyte chemoattractant protein-1 and KC production in the zymosan peritonitis model. Removal of Mφ augmented the accumulation of PMN elicited by the latter stimulus. This was due to an inhibitory action of Mφ-derived IL-10 because there was 1) a time- dependent release of IL-10 in the zymosan exudates; 2) a reduction in IL-10 levels following Mφ, but not MC, depletion; and 3) an increased PMN influx and chemokine production in IL-10 knockout mice. In conclusion, we propose a stimulus-dependent role of resident MCs in chemokine production and the existence of a regulatory loop between endogenous IL-10 and the chemokine- mediated cellular component of acute inflammation.

Original languageEnglish
Pages (from-to)1685-1691
Number of pages7
JournalJournal of Immunology
Volume162
Issue number3
Publication statusPublished - Feb 1 1999

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Peritoneal Macrophages
Chemokines
Mast Cells
Interleukin-10
Neutrophils
Inflammation
Zymosan
Thioglycolates
Chemokine CCL2
p-Methoxy-N-methylphenethylamine
Therapeutic Irrigation
Peritoneal Cavity
Diphosphonates
Exudates and Transudates
Peritonitis
Knockout Mice
Liposomes
Suspensions
Cell Count
Macrophages

ASJC Scopus subject areas

  • Immunology

Cite this

Role of resident peritoneal macrophages and mast cells in chemokine production and neutrophil migration in acute inflammation : Evidence for an inhibitory loop involving endogenous IL-10. / Ajuebor, Maureen N.; Das, Anuk M.; Virag, L.; Flower, Roderick J.; Szabó, Csaba; Perretti, Mauro.

In: Journal of Immunology, Vol. 162, No. 3, 01.02.1999, p. 1685-1691.

Research output: Contribution to journalArticle

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