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Prepublished online as a Blood First Edition Paper on August 15, 2002; DOI 10.1182/blood-2002-03-0921.
Submitted March 25, 2002
Accepted August 6, 2002
Early macrophage influx to sites of cutaneous granuloma formation is dependent on MIP-1 /ß released from neutrophils recruited by mast cell-derived TNF
Esther von Stebut, Martin Metz, Genevieve Milon, Juergen Knop, and Marcus Maurer*
Department of Dermatology, Johannes Gutenberg University, Mainz, Germany
Unite d'Immunophysiologie et Parasitisme Intracellulaire, Institut Pasteur, Paris, France
* Corresponding author; email: maurer{at}hautklinik.klinik.uni-mainz.de.
Macrophages (M ) play a crucial role in the development of cutaneous granulomas (CG) initiated by foreign bodies or invasive microorganisms. However, little is known about how M are recruited to sites of CG formation. To test whether mast cells (MC) contribute to
early M recruitment to developing granulomas, CG were induced in MC-deficient KitW/KitW-v mice by injection of polyacrylamide gel (PAG). KitW/KitW-v mice as well as mice deficient for the MC-product TNF exhibited markedly reduced M numbers in CG. M recruitment was restored in KitW/KitW-v mice reconstituted with MC from Kit+/+ or TNF+/+, but not from TNF-/- mice. MC-TNF-dependent M influx required prior recruitment of MIP-1/ß-producing neutrophils (PMN), as PMN-depletion before induction of CG completely inhibited M influx, which was restored after reconstitution with PMN-supernatants. These
findings indicate that M recruitment to cutaneous PAG-induced granulomas is the result of a sequence of
inflammatory events initiated by MC-derived TNF followed by PMN influx and MIP-1/ß release.
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