title: Large and sustained induction of chemokines during impaired wound healing in the genetically diabetic mouse: prolonged persistence of neutrophils and macrophages during the late phase of repair.
abstract: Chemokines are seen as the stimuli that largely control leukocyte migration. To assess whether the severely impaired process of cutaneous repair observed in genetically diabetic db/db mice is associated with a dysregulated infiltration of immune cells, we determined the expressional kinetics for the murine growth-regulated oncogene/melanoma growth stimulatory activity homolog macrophage inflammatory protein-2, and the macrophage chemoattractant protein-1, respectively. Wound repair in db/db mice was characterized by a sustained inflammatory response and a prolonged expression of macrophage inflammatory protein-2 and macrophage chemoattractant protein-1. Immuno-histochemistry revealed that keratinocytes at the wound margins expressed macrophage chemoattractant protein-1, whereas macrophage inflammatory protein-2 immunopositive signals were observed only in keratinocytes of hair follicles located adjacent to the wound site. Inactivation studies using neutralizing antibodies against macrophage chemoattractant protein-1 or macrophage inflammatory protein-2 indicated that sustained expression of these chemokines participated in a prolonged presence of neutrophils and macrophages at the wound site during diabetic repair. Furthermore, our data provide evidence that late infiltration (day 13 after injury) of neutrophils and macrophages into wounds in db/db mice was associated with a simultaneous downregulation of mRNA for receptors specific for macrophage inflammatory protein-2 and macrophage chemoattractant protein-1 in these animals.
authors.affiliation: Zentrum der Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Wetzler
authors.forename: H
authors.initials: H
authors.lastname: Kämpfer
authors.forename: B
authors.initials: B
authors.lastname: Stallmeyer
authors.forename: J
authors.initials: J
authors.lastname: Pfeilschifter
authors.forename: S
authors.initials: S
authors.lastname: Frank
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism*; D003872:Dermatitis / Q000209:etiology / Q000473:pathology; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015536:Down-Regulation; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D009504:Neutrophils / Q000473:pathology / Q000502:physiology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D023063:Receptors, Interleukin-8B; D012867:Skin / Q000293:injuries*; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000150:complications / Q000473:pathology / Q000503:physiopathology*
chemical_list: C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D023063:Receptors, Interleukin-8B