title: The relationship between collagen scaffold cross-linking agents and neutrophils in the foreign body reaction.
abstract: In order to get more insight into the role of neutrophils on the micro-environment and consequently on macrophages in the foreign body reaction in mice, we investigated the fate of the two differently cross-linked dermal sheep collagen disks (glutaraldehyde = GDSC, hexamethylenediisocyanate = HDSC) in mice implanted in one anatomical location, namely subcutaneously. In GDSC massive infiltration of neutrophils is seen at day 2 and day 21, whereas in HDSC only minor infiltration is seen at day 2. The presence of neutrophils coincided with high levels of IFN-γ, a cytokine that activates macrophages. Major differences were seen in degradation rate of the two disks: GDSC was almost completely degraded after 28 days, whereas HDSC remained intact. Degradation of GDSC occurred through collagenolytic activity and phagocytosis by macrophages. Phagocytosis was observed at day 2 and day 21. IL-13 was only observed in HDSC, and this resulted in the presence of giant cells in HDSC. These giant cells produced IL-10, that promoted TIMP-1 expression and that inhibits collagenolytic and phagocytic activity. We conclude that the function of macrophages in mice is largely influenced by differences in micro-environment induced by GDSC and HDSC and that the presence/absence of neutrophils play a major role in the shaping of this micro-environment.
authors.affiliation: Stem Cell & Tissue Engineering Research Group, Medical Biology Section, Department of Pathology & Medical Biology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, Groningen, The Netherlands. qingsongye@hotmail.com
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Ye
authors.forename: Martin C
authors.initials: MC
authors.lastname: Harmsen
authors.forename: Marja J A
authors.initials: MJ
authors.lastname: van Luyn
authors.forename: Ruud A
authors.initials: RA
authors.lastname: Bank
mesh_terms: D000818:Animals; D003094:Collagen / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology*; D005549:Foreign-Body Reaction / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism*; D015726:Giant Cells / Q000378:metabolism; D005976:Glutaral / Q000737:chemistry / Q000494:pharmacology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D017953:Isocyanates / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects; D012756:Sheep; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D018793:Interleukin-13; D017953:Isocyanates; D019715:Tissue Inhibitor of Metalloproteinase-1; D016753:Interleukin-10; D007371:Interferon-gamma; D003094:Collagen; D005976:Glutaral