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wound site. The initial population of white blood cells elicited by injury are only helpful to the healing process if
[15]
in the wound is composed of neutrophils. Thrombin they are timely and transient. However, the inflammation
[34]
and IL‑8 stimulate endothelial permeability through is not essential for skin wound healing. Martin et al. has
the modulations of adherens‑junction endothelial cell shown that the PU.1 null mouse, which is devoid of both
adhesion and cell contraction, thereby facilitating macrophages and neutrophils, healed both incisional and
leukocyte exit from the circulation. [16,17] Within the excisional wounds at statistically similar rates to wild‑type
wound, neutrophils employ various strategies to kill littermates, but without scar formation. The cytokine and
bacteria and decontaminate the wound, including the growth‑factor profiles at the wound site in the PU.1 null
secretion of proteases and antimicrobial peptides, as well mouse differed from those of the wild‑type. As a result, cell
as the generation of reactive oxygen intermediates via death was reduced, and scar formation did not occur.
[34]
the respiratory burst. In the absence of inflammatory Studies have focused on platelets and mast cells as targets,
[18]
mediators, neutrophils will undergo spontaneous and have shown that neither of these mediators is essential
apoptosis. The apoptosis is mediated by cathepsin D to effective wound repair. This further suggests that a
release from neutrophil granules, which then facilitates dampened or modified inflammatory response could reduce
the cleavage and activation of caspase 8, ultimately scar formation. [13,35] Impairment of macrophage function
resulting in caspase 3 activation, DNA fragmentation and at the wound site derails the resolution of inflammation.
[19]
apoptosis. In the absence of neutrophils, wound site A persistent inflammatory state of diabetic wound
macrophages lack guidance in conducting the healing macrophages is caused by impairment in the ability of these
process. Although neutrophils play a role in decreasing cells to phagocytose apoptotic cells at the wound site, in
[20]
infection during wound healing, their absence does not turn preventing the switch from M1 to M2 phenotype.
[36]
prevent the overall progress of wound healing. However, Prolonged inflammation may not only compromise wound
[21]
their prolonged presence in the wound may be a factor in closure but may also worsen scar outcomes. [37,38] Lipid
the conversion of acute wounds into nonhealing chronic mediators, such as the lipoxins, resolvins, protectins and
wounds. maresins, have emerged as a novel genus of potent and
Within two to three days, monocytes become the stereoselective players that counter regulate excessive
predominant inflammatory cell population in the wound. acute inflammation and stimulate molecular and cellular
[39]
Monocyte chemotaxis to the wound occurs via CC events that define resolution. The production and
chemokines like CCL2. The chemokines can be released activity of several proteases including metalloproteinase,
by neutrophils, by the monocytes themselves and by serine proteases and neutrophil elastases which are tightly
keratinocytes at different stages of healing. [22‑24] Circulating regulated in acute wound healing may be altered in
[1]
monocytes and mast cells are attracted to and infiltrate the chronic wounds. For example, non‑healing human wound
wound site. [1,25] Within the wound, monocytes differentiate fluid and tissue have increased protease activity, which
into macrophages. Macrophages in turn remove rapidly degrades exogenously applied peptide growth
apoptotic neutrophils and other dead cells, function as factors. [40,41] Products targeting excessive protease activity
antigen‑presenting cells, and secrete cytokines and multiple such as protease‑scavenging matrices (e.g. Promogran),
peptide growth factors. Phagocytosis of the apoptotic selective inhibitors or specific antibodies may be useful in
[10]
neutrophils by macrophages then leads to removal of the treatment of chronic wounds refractory to conventional
chemokines from the area of inflammation, preventing treatments. [42,43]
further leukocyte influx. Several cytokines and growth The lymphocytes are the last type of leukocytes to arrive
[10]
factors are known to be secreted by macrophages. Such at the wound site. The lymphocytes exert a specific
[26]
growth factors include TGF‑b, TGF‑α, basic FGF (bFGF), response against microbes and other foreign material
VEGF and PDGF. These growth factors activate and attract in the wound: B‑lymphocytes via antibodies and the
local endothelial cells, fibroblasts and keratinocytes, and T‑lymphocytes through production of cytokines and
enable wound healing by causing cell proliferation and stimulation of cytolytic activity. Lymphocyte‑induced
synthesis of ECM and inducing angiogenesis VEGF, [27‑30] inflammation is then resolved by apoptosis when
which stimulates angiogenesis, also stimulates the interferon (IFN)‑c and TNF‑α are produced at the wound
macrophages to express LIGHT, a member of the tumor site. Mast cells also appear during the later part of the
[10]
necrosis factor alpha (TNF‑α) family of cytokines, which inflammatory phase, but their function remains unclear.
binds to lymphotoxin‑b receptor and induces macrophage Impaired wound healing has been reported in mast
death. [31] cell‑deficient mice. Mast cells have also been implicated
[44]
Macrophages play a crucial role in enabling wound healing. in skin wound fibrosis. [45,46] Recently, the role of mast cells
Macrophage depletion is known to markedly impair wound in wound healing has become an area of intense research
[33]
closure. [27,32] In a landmark study, Leibovich and Ross because of a correlation between mast cells and both
demonstrated that the antimacrophage serum combined keloids and hypertrophic scars. [45,46]
with hydrocortisone diminished the accumulation of
macrophages in healing skin wounds of adult guinea pigs. PROLIFERATION PHASE
Such depletion resulted in impaired disposal of damaged
tissue and provisional matrix, compromised fibroblast The proliferative phase of wound healing is accepted to
count, and delayed healing. Inflammatory responses start around two days after injury and typically lasts up

252 Plast Aesthet Res || Vol 2 || Issue 5 || Sep 15, 2015