The neutrophilic leukocyte in wound repair

Abstract

A B S T R A C T The role of the neutrophilic leukocyte in wound healing was investigated by observing the progress of repair in the absence of these cells. Circulating neutrophils were eliminated in guinea pigs by the administration of antineutrophil serum (ANS) 24 hr before wounding and by daily injections throughout a 10 day period of healing. Control animals received normal rabbit serum at the same dose levels and times. The wounds consisted of six linear incisions in the dorsal skin of the animals.The contents of 24-hr neutropenic and control wounds were compared by quantitating the major cellular and extracellular wound components using a histometric technique. At 24 hr, there were no differences between control and neutropenic wounds in the per cent of total wound volume occupied by mononuclear leukocytes and fibrin. The neutropenic wounds had no neutrophils, had a significantly decreased volume of fluid space, and an increased volume of red cells, as compared with controls. The differences in numbers of erythrocytes and amount of fluid space in these two sets of wounds may be related to substances within neutrophils that promote lysis of erythrocytes or affect vascular permeability.In spite of the lack of neutrophils in the ANS-treated animals during the 10 days of healing, no differences were observed between the control and neutropenic wounds relative to the rate of wound debridement or the extent of repair. The wounds from the two groups of animals were identical in cellularity and degree of connective tissue formation.These observations support the notion that neither wound debridement nor the formation of granulation tissue are dependent upon the presence of neutrophils. A neutrophil response in early wounds is not an essential antecedent to the infiltration of monocytes, as suggested by previous investigations.

Neutrophil depletion delays wound repair in aged mice

“…In young mice, the findings are quite similar to those done using anti-neutrophil serum (ANS) (Simpson and Ross 1972). Why, then, does neutrophil depletion delay wound healing in old mice?…”

“…Classical experiments in the 1970's directly tested neutrophil and macrophage function by depleting them by antisera in a guinea pig wound model. These experiments showed that antisera depletion of neutrophils seemed not to perturb tissue repair, but depletion of macrophages with antisera and steroids resulted in a failure of debridement (Leibovich and Ross 1976;Leibovich and Ross 1975;Simpson and Ross 1972). More recent neutrophil knockdown experiments in mice using specific anti-mouse neutrophil antibodies support the depletion studies conducted in the 1970s.…”

Differential Roles of Macrophages in Diverse Phases of Skin Repair

“…The role of macrophages during skin repair has remained a subject of debate due to their functional dichotomy as effectors of both tissue injury and repair (33). Furthermore, in earlier studies of skin injury, macrophages have been depleted by administration of antimacrophage serum and/or hydrocortisone, methods that have pleiotropic effects and lead to unspecific and partial cell depletion (10,11). To circumvent these difficulties, we used a transgenic mouse line, LysMCre/iDTR, in which minute amounts of DT can efficiently, specifically, and in a timely restricted manner deplete tissue-resident and inflammatory macrophages recruited to the site of skin injury.…”

“…Experiments in the 1970s established the concept that under sterile conditions, the influx of macrophages is essential for efficient healing of incisional skin wounds, whereas the influx of neutrophils might not be crucial (10,11). This dogma has been challenged by recent reports, thereby arguing against an essential role of inflammatory cells in wound repair: early fetal wounds heal with minimal scarring, which is associated with little inflammation (12).…”

The immune system and cardiac repair

“…Although the contribution of the neutrophil to fibrous tissue deposition in the healing infarct cannot be excluded; it is unlikely that this cell type plays a critical role in the events leading to formation of a scar. In a study performed more than thirty years ago, Simpson and Ross demonstrated that depletion of circulating neutrophils in guinea pigs treated with antineutrophil serum had no effects on granulation tissue formation in a model of cutaneous healing, suggesting that the neutrophil response may not be essential in the repair process [214]. Neutrophils may contribute to the healing response through their apoptosis and subsequent clearance by macrophages; this process, as will be discussed later, releases TGF-β, resulting in resolution of inflammation and transition to fibrosis.…”