Mast cells modulate the inflammatory but not the proliferative response in healing wounds

Wound Repair and Regeneration - Tập 11 Số 1 - Trang 46-54 - 2003
Eric I. Egozi1, Ahalia M. Ferreira1, Aime L. Burns1, Richard L. Gamelli1, Luisa A. DiPietro1
1From the Burn and Shock Trauma Institute, Department of Surgery, Loyola University Medical Center, Maywood, Illinois.

Tóm tắt

Upon stimulation, mast cells release a heterogeneous group of factors that promote inflammation and influence cell proliferation. Mast cells accumulate at sites of injury, further suggesting a critical role in wound healing. To assess the importance of mast cells in tissue repair, we compared wound healing in mast cell–deficient WBB6F1/J‐KitW/KitW–v (KitW/KitW–v) and wild type WBB6F1/++ (WT) mice. During the inflammatory phase, neutrophil infiltration into wounds of the KitW/KitW–v mice was significantly less than that of WT mice (84.6 ± 10.3 vs. 218 ± 26.0 cells/10 high‐power fields at day 3, p < 0.001), while wound macrophage and T cell infiltration were similar in both strains. The decrease in neutrophils could not be explained by changes in tumor necrosis factor‐α or macrophage inflammatory protein‐2 levels, because the amounts of these two neutrophil chemoattractants were similar in both KitW/KitW–v and WT mice. Surprisingly, the absence of mast cells had no effect on the proliferative aspects of wound healing, including reepithelialization, collagen synthesis, and angiogenesis. Although mast cells are known to release proangiogenic mediators, vascular endothelial growth factor levels were similar in WT and KitW/KitW–v mice. Moreover, levels of fibroblast growth factor‐2 were increased in KitW/KitW–v mice (4206 ± 107 vs. 1865 ± 249 pg/ml, p < 0.01). These results suggest that mast cells modulate the recruitment of neutrophils into sites of injury, yet indicate that mast cells are unlikely to exert a major influence on the proliferative response within healing wounds. (WOUND REP REG 2003;11:46–54)

Từ khóa


Tài liệu tham khảo

10.1097/00062752-200001000-00007

10.1111/j.1365-2133.1983.tb00060.x

10.1002/(SICI)1096-9896(200001)190:1<100::AID-PATH496>3.0.CO;2-Q

10.1016/S0733-8635(18)30221-3

10.1016/S0039-6109(16)40983-7

10.1128/iai.65.9.3501-3508.1997

Schwartz LB, 1984, Structure and function of the chemical mediators of mast cells, Prog Allergy, 34, 271

10.1038/346274a0

10.1073/pnas.88.10.4220

Williams CM, 1995, Induced expression of mRNA for IL‐5, IL‐6, TNF‐alpha, MIP‐2 and IFN‐ gamma in immunologically activated rat peritoneal mast cells: inhibition by dexamethasone and cyclosporin A, Immunology, 86, 244

Moller A, 1993, Human mast cells produce IL‐8, J Immunol, 151, 3261, 10.4049/jimmunol.151.6.3261

10.1038/381077a0

10.1084/jem.192.10.1441

10.1083/jcb.39.1.152

Simpson DM, 1971, Effects of heterologous antineutrophil serum in guinea pigs. Hematologic and ultrastructural observations, Am J Pathol, 65, 79

Leibovich SJ, 1975, The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum, Am J Pathol, 78, 71

10.1097/00024382-199510000-00001

10.1016/S0030-6665(20)30469-2

10.1046/j.1365-2168.1998.00734.x

10.1111/j.1600-0625.1999.tb00342.x

10.1080/08941930290085903

Marks RM, 1986, Mast cell granules cause proliferation of human microvascular endothelial cells, Lab Invest, 55, 289

Norrby K, 1997, Mast cells and de novo angiogenesis: angiogenic capability of individual mast‐cell mediators such as histamine, TNF, IL‐8 and bFGF, Inflamm Res, 46, S7, 10.1007/PL00022372

Meininger CJ, 1992, Mast cells and angiogenesis, Semin Cancer Biol, 3, 73

10.1002/ijc.2910180520

10.1182/blood.V86.7.2488.2488

Reed JA, 1995, Human cutaneous mast cells express basic fibroblast growth factor, Lab Invest, 72, 215

Qu Z, 1995, Mast cells are a major source of basic fibroblast growth factor in chronic inflammation and cutaneous hemangioma, Am J Pathol, 147, 564

10.1091/mbc.9.4.875

10.1007/s004180050328

10.1084/jem.188.6.1135

10.1084/jem.176.5.1375

10.1016/S0039-6060(96)80148-6

Nissen NN, 1998, Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing, Am J Pathol, 152, 1445

10.1073/pnas.95.10.5672

10.1084/jem.152.4.931

10.1172/JCI119458

10.1016/S0014-2999(00)00350-2

10.1172/JCI119290

Cairns JA, 1996, Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL‐ 8 production and intercellular adhesion molecule‐1 expression, J Immunol, 156, 275, 10.4049/jimmunol.156.1.275

10.1016/0003-9861(61)90291-0

Swift ME, 1999, Impaired wound repair and delayed angiogenesis in aged mice, Lab Invest, 79, 1479

10.1074/jbc.270.9.4689

10.1111/1523-1747.ep12581221

10.1053/gast.1996.v110.pm8613053

Qureshi R, 1988, The role of mast cells in thioglycollate‐induced inflammation, J Immunol, 141, 2090, 10.4049/jimmunol.141.6.2090

Zhang Y, 1992, Mast cells enhance the antibody‐mediated injury of skin basement membrane in mice, J Immunol, 149, 2482, 10.4049/jimmunol.149.7.2482

10.1111/j.1699-0463.1999.tb01493.x

10.1126/science.1470922

Ajuebor MN, 1999, Role of resident peritoneal macrophages and mast cells in chemokine production and neutrophil migration in acute inflammation: evidence for an inhibitory loop involving endogenous IL‐10, J Immunol, 162, 1685, 10.4049/jimmunol.162.3.1685

10.1073/pnas.86.22.8972

10.1007/s000110050599

10.1006/bbrc.1994.2287