title: Restraint stress alters neutrophil and macrophage phenotypes during wound healing.
abstract: Previous studies reported that stress delays wound healing, impairs bacterial clearance, and elevates the risk for opportunistic infection. Neutrophils and macrophages are responsible for the removal of bacteria present at the wound site. The appropriate recruitment and functions of these cells are necessary for efficient bacterial clearance. In our current study we found that restraint stress induced an excessive recruitment of neutrophils extending the inflammatory phase of healing, and the gene expression of neutrophil attracting chemokines MIP-2 and KC. However, restraint stress did not affect macrophage infiltration. Stress decreased the phagocytic abilities of phagocytic cells ex vivo, yet it did not affect superoxide production. The cell surface expression of adhesion molecules CD11b and TLR4 were decreased in peripheral blood monocytes in stressed mice. The phenotype of macrophages present at the wound site was also altered. Gene expression of markers of pro-inflammatory classically activated macrophages, CXCL10 and CCL5, were down-regulated; as were markers associated with wound healing macrophages, CCL22, IGF-1, RELMα; and the regulatory macrophage marker, chemokine CCL1. Restraint stress also induced up-regulation of IL10 gene expression. In summary, our study has shown that restraint stress suppresses the phenotype shift of the macrophage population, as compared to the changes observed during normal wound healing, while the number of macrophages remains constant. We also observed a general suppression of chemokine gene expression. Modulation of the macrophage phenotype could provide a new therapeutic approach in the treatment of wounds under stress conditions in the clinical setting.
authors.affiliation: Department of Periodontics, Center for Wound Healing and Tissue Regeneration, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Stéphanie D
authors.initials: SD
authors.lastname: Tymen
authors.forename: Isolde G
authors.initials: IG
authors.lastname: Rojas
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhou
authors.forename: Zong Juan
authors.initials: ZJ
authors.lastname: Fang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Phillip T
authors.initials: PT
authors.lastname: Marucha
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000502:physiology; D054402:Chemokine CCL1 / Q000502:physiology; D018946:Chemokine CCL5 / Q000502:physiology; D054357:Chemokine CXCL10 / Q000502:physiology; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008812:Mice, Hairless; D009504:Neutrophils / Q000502:physiology*; D010641:Phenotype; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000502:physiology; D014945:Wound Healing / Q000276:immunology* / Q000502:physiology
chemical_list: D039481:CD11b Antigen; C502258:Ccl1 protein, mouse; C503460:Ccl5 protein, mouse; D054402:Chemokine CCL1; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D007334:Insulin-Like Growth Factor I