Impaired healing of nitrogen mustard wounds in CXCR2 null mice.
To examine the significance of chemokine activation of CXCR2 in wound healing after chemical burn, cutaneous injury was created by topical application of nitrogen mustard on CXCR2 wild type (+/+), heterozygous (+/-), and knockout (-/-) mice. Wounds were analyzed histologically for neutrophil and monocyte infiltration and for reepithelialization at postwound days 4, 7, and 10. Neutrophil recruitment to the wound site was reduced through postwound day 7 in CXCR2 -/- mice as indicated by myeloperoxidase assay and by visual quantitation. Because there is always concern that mice with targeted deletion of a specific receptor may undergo developmental adaptations to offset the loss of the receptor, we also accessed chemical wound repair in the presence of a small molecule antagonist of CXCR2. Dietary supplementation with a CXCR2 antagonist (SB-265610) during the wound repair process also markedly delayed healing parameters in CXCR2 +/+ mice, even greater than treatment with glucocorticoids. These parallel studies further establish that mice deficient in CXCR2 function exhibit delayed cutaneous wound healing that may be primarily linked to impaired neutrophil recruitment after chemical burn with nitrogen mustard. Thus, there may be a potential therapeutic benefit of treating nitrogen mustard-induced skin lesions with agonists of CXCR2 to facilitate the wound repair process.
Milatovic
Snjezana
S
Department of Cancer Biology, Vanderbilt University School of Medicine, and Department of Veterans Affairs, Nashville, Tennessee 37232, USA.
Nanney
Lillian B
LB
Yu
Yingchun
Y
White
John R
JR
Richmond
Ann
A
D000818:Animals; D002057:Burns, Chemical / Q000503:physiopathology*; D008466:Mechlorethamine; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout / Q000235:genetics; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011239:Prednisolone / Q000494:pharmacology; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000473:pathology / Q000503:physiopathology
D019707:Receptors, Chemokine; D023063:Receptors, Interleukin-8B; D008466:Mechlorethamine; D011239:Prednisolone; D009195:Peroxidase