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PMID: 10951241 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Delayed wound healing in CXCR2 knockout mice.

The Journal of investigative dermatology ·Vol. 115 ·No. 2 ·2000-08-00 ·Pages 234-44

Devalaraja RM, Nanney LB, Du J, Qian Q, Yu Y, Devalaraja MN, Richmond A

Abstract

Previous studies demonstrated that the CXC chemokine, MGSA/GRO-alpha and its receptor, CXCR2, are expressed during wound healing by keratinocytes and endothelial cells at areas where epithelialization and neovascularization occur. The process of wound healing is dependent on leukocyte recruitment, keratinocyte proliferation and migration, and angiogenesis. These processes may be mediated in part by CXC chemokines, such as interleukin-8 and MGSA/GRO-alpha. To examine further the significance of CXC chemokines in wound healing, full excisional wounds were created on CXCR2 wild-type (+/+), heterozygous (+/-), or knockout (-/-) mice. Wounds were histologically analyzed for neutrophil and monocyte infiltration, neovascularization and epithelialization at days 3, 5, 7, and 10 postwounding. The CXCR2 -/- mice exhibited defective neutrophil recruitment, an altered temporal pattern of monocyte recruitment, and altered secretion of interleukin-1beta. Significant delays in wound healing parameters, including epithelialization and decreased neovascularization, were also observed in CXCR2 -/- mice. In vitro wounding experiments with cultures of keratinocytes established from -/- and +/+ mice revealed a retardation in wound closure in CXCR2 -/- keratinocytes, suggesting a role for this receptor on keratinocytes in epithelial resurfacing that is independent of neutrophil recruitment. These in vitro and in vivo studies further establish a pathophysiologic role for CXCR2 during cutaneous wound repair.

MeSH Terms
Animals Cell Movement/physiology Cytokines/metabolism Keratinocytes/physiology Mice Mice, Inbred BALB C Mice, Knockout/genetics Monocytes/physiology Neovascularization, Physiologic/physiology Neutrophils/physiology Receptors, Chemokine/genetics,physiology Receptors, Interleukin/genetics,physiology Receptors, Interleukin-8B Skin/injuries,pathology Time Factors Wound Healing/physiology Wounds and Injuries/pathology,physiopathology
Chemicals
Cytokines Receptors, Chemokine Receptors, Interleukin Receptors, Interleukin-8B
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Devalaraja R M
Departments of Cell Biology, Plastic Surgery, Medicine (Division of Dermatology), Vanderbilt University School of Medicine and Department of Veterans Affairs, Nashville, Tennessee 37232, USA.
Nanney L B
Du J
Qian Q
Yu Y
Devalaraja M N
Richmond A
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Article Info
Journal
The Journal of investigative dermatology
Abbr.
J Invest Dermatol
ISSN
0022-202X
DOI
10.1046/j.1523-1747.2000.00034.x
Published
2000-08-00
Pages
234-44
Language
English
Region
United States
NLM ID
0426720
PMCID
PMC2664868
Subset
IM
Grants
BLRD VA · IK6 BX005225 · United States
NCI NIH HHS · CA34590 · United States
NCI NIH HHS · R01 CA034590-17 · United States
NCI NIH HHS · R01 CA034590 · United States
NCI NIH HHS · P30 CA068485 · United States
NIAMS NIH HHS · 5P30AR4194 · United States
NCI NIH HHS · CA68485 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1046/j.1523-1747.2000.00034.x PMC Full Text View journal details
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