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.
The roles played by resident macrophages (Mphi) 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 Mphi 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 Mphi 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 Mphi augmented the accumulation of PMN elicited by the latter stimulus. This was due to an inhibitory action of Mphi-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 Mphi, 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.
Ajuebor
M N
MN
Department of Biochemical Pharmacology, The William Harvey Research Institute, London, United Kingdom.
Das
A M
AM
Virág
L
L
Flower
R J
RJ
Szabó
C
C
Perretti
M
M
D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D054360:Chemokine CXCL1; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D007249:Inflammation / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology / Q000502:physiology*; D010538:Peritonitis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction