Julien Succar1, Giorgio Giatsidis1, Nanze Yu1, Kazi Hassan1, Roger Khouri1, Michael F Gurish2, Gunnar Pejler3,4, Magnus Åbrink5, Dennis Paul Orgill1. 1. Tissue Engineering and Wound Healing Laboratory, Division of Plastic Surgery, Department of Surgery Brigham and Women's Hospital-Harvard Medical School, Boston, Massachusetts. 2. Human Immunology Center, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital-Harvard Medical School, Boston, Massachusetts. 3. Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. 4. Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden. 5. Section of Immunology, Department of Biomedical Sciences & Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Abstract
Objective: Mouse mast cell protease-4 (mMCP-4, also known as chymase) has both pro- and anti-inflammatory roles depending on the disease model. However, its effects have not been studied in surgically wounded skin. Given the significant clinical applications of modulating the inflammatory response in wound healing, we examined the role of mMCP-4 and the effect of its inhibitor chymostatin on leukocyte and polymorphonuclear cell (PMN) recruitment in our skin model. Approach: Recruitment was assessed on day-1 postwounding of three groups of mice (n = 10 each): mMCP-4 null mice, wild-type (WT) mice treated with the mMCP-4 inhibitor chymostatin, and WT with no other intervention. Leukocytes were stained with CD-45 cell marker, and PMN cells were stained with chloroacetate esterase. Results: The WT mice had 27 ± 9 leukocytes per field compared with 11 ± 6 for the mMCP-4 nulls, a decrease of 60% (p = 0.03), whereas the chymostatin-injected group had a count comparable with the uninjected WT controls at 24 ± 9. The WT group had a PMN count of 96 ± 12 cells, compared with just 24 ± 8 in the mMCP-4 null group, a decrease of 75% (p = 0.001), whereas the chymostatin-treated group had 60 ± 18 cells, a decrease of 38% compared with the WT group (p = 0.03). Innovation: We showed that the inflammatory process can be influenced by impeding the arrival of PMNs into the surgically injured site using the mMCP-4 inhibitor chymostatin. Conclusion: Chymase contributes to the recruitment of white blood cells in surgically wounded skin.
Objective: Mousemast cell protease-4 (mMCP-4, also known as chymase) has both pro- and anti-inflammatory roles depending on the disease model. However, its effects have not been studied in surgically wounded skin. Given the significant clinical applications of modulating the inflammatory response in wound healing, we examined the role of mMCP-4 and the effect of its inhibitor chymostatin on leukocyte and polymorphonuclear cell (PMN) recruitment in our skin model. Approach: Recruitment was assessed on day-1 postwounding of three groups of mice (n = 10 each): mMCP-4 null mice, wild-type (WT) mice treated with the mMCP-4 inhibitor chymostatin, and WT with no other intervention. Leukocytes were stained with CD-45 cell marker, and PMN cells were stained with chloroacetate esterase. Results: The WT mice had 27 ± 9 leukocytes per field compared with 11 ± 6 for the mMCP-4 nulls, a decrease of 60% (p = 0.03), whereas the chymostatin-injected group had a count comparable with the uninjected WT controls at 24 ± 9. The WT group had a PMN count of 96 ± 12 cells, compared with just 24 ± 8 in the mMCP-4 null group, a decrease of 75% (p = 0.001), whereas the chymostatin-treated group had 60 ± 18 cells, a decrease of 38% compared with the WT group (p = 0.03). Innovation: We showed that the inflammatory process can be influenced by impeding the arrival of PMNs into the surgically injured site using the mMCP-4 inhibitor chymostatin. Conclusion:Chymase contributes to the recruitment of white blood cells in surgically wounded skin.
Authors: Nora Céspedes; Erinn L Donnelly; Casey Lowder; Gretchen Hansten; Delaney Wagers; Anna M Briggs; Joseph Schauer; Lori Haapanen; Magnus Åbrink; Judy Van de Water; Shirley Luckhart Journal: Front Immunol Date: 2022-01-27 Impact factor: 7.561