title: MIP-1alpha as a critical macrophage chemoattractant in murine wound repair.
abstract: At sites of injury, macrophages secrete growth factors and proteins that promote tissue repair. While this central role of the macrophage has been well studied, the specific stimuli that recruit macrophages into sites of injury are not well understood. This study examines the role of macrophage inflammatory protein 1alpha (MIP-1alpha), a C-C chemokine with monocyte chemoattractant capability, in excisional wound repair. Both MIP-1alpha mRNA and protein were detectable in murine wounds from 12 h through 5 d after injury. MIP-1alpha protein levels peaked 3 d after injury, coinciding with maximum macrophage infiltration. The contribution of MIP-1alpha to monocyte recruitment into wounds was assessed by treating mice with neutralizing anti-MIP-1alpha antiserum before injury. Wounds of mice treated with anti-MIP-1alpha antiserum had significantly fewer macrophages than control (41% decrease, P < 0. 01). This decrease in wound macrophages was paralleled by decreased angiogenic activity and collagen synthesis. When tested in the corneal micropocket assay, wound homogenates from mice treated with anti-MIP-1alpha contained significantly less angiogenic activity than control wound homogenates (27% positive for angiogenic activity versus 91% positive in the control group, P < 0.01). Collagen production was also significantly reduced in the wounds from anti-MIP-1alpha treated animals (29% decrease, P < 0.05). The results demonstrate that MIP-1alpha plays a critical role in macrophage recruitment into wounds, and suggest that appropriate tissue repair is dependent upon this recruitment.
authors.affiliation: Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois 60153, USA. Idipiet@luc.edu
authors.forename: L A
authors.initials: LA
authors.lastname: DiPietro
authors.forename: M
authors.initials: M
authors.lastname: Burdick
authors.forename: Q E
authors.initials: QE
authors.lastname: Low
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
mesh_terms: D000818:Animals; D001483:Base Sequence; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002633:Chemotaxis / Q000502:physiology; D003094:Collagen / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D005260:Female; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017931:DNA Primers; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D003094:Collagen