title: Identification of a human dermal macrophage population responsible for constitutive restraint of primary dermal fibroblast proliferation.
abstract: Primary human dermal cell suspensions prepared from the papillary dermis of keratomed skin strips were used to investigate the effect of indigenous dermal macrophages (HLA-DR+, CD11c+ CD11b+ CD1c- phagolysosome+) upon dermal fibroblast proliferation. Rapid dermal fibroblast expansion was induced upon immunomagnetic bead removal of CD11b+ or CD11c+ cells as well as by removal of more inclusive subsets contained within the DR+ population, but the removal of mast cells, endothelial cells, and CD1c+ dermal Langerhans cells from dermal cell suspensions failed to result in proliferation of the remaining cell subsets. Removal of 1B10+ fibroblasts from macrophage depleted (CD11b-) dermal cell suspensions essentially abrogated the unrestrained proliferation of the CD11b- dermal cells. Flow cytometric cell cycle analysis of cultured macrophage-depleted dermal cells confirmed that the unrestrained proliferating cells contain procollagen I+ as well as procollagen I- dermal fibroblasts. Inhibition of primary fibroblast expansion by adding a supernatant from unfractionated dermal cells suggested that a growth-inhibitory soluble activity of >30,000 kDa dominates the cytokine mixture released by unfractionated fresh dermal cells ex vivo. Inhibitory activity counterbalanced positive fibroblast growth- stimulatory cytokines released by dermal cells because neutralizing antibodies to insulin-like growth factor 1 and interleukin-1 beta resulted in decreased CD11b- dermal cell fibroblast proliferation. These data indicated an important role for dermal macrophages of the DR+ CD11b+ CD11c+ DC1c- phenotype in the normal homeostatic restraint of primary human dermal fibroblast proliferation.
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez-Ramos
authors.forename: K D
authors.initials: KD
authors.lastname: Cooper
authors.forename: C
authors.initials: C
authors.lastname: Hammerberg
mesh_terms: D000328:Adult; D018845:CD11 Antigens / Q000032:analysis; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D012867:Skin / Q000166:cytology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018845:CD11 Antigens; D006684:HLA-DR Antigens; D016898:Interferon-alpha; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I