GROWTH INDUCED BY DAMAGE
13
most experimental animals it is the loose areolar connective tissue in
the subcutis, and beneath the layer of skin muscle, the panniculus
carnosus, that are the primary sources of the granulation tissue (Grillo,
1964; Russell and Billingham, 1962), although it is still possible that some
of the granulation tissue arises from cells that migrate into the wound via
the blood vessels and differentiate into fibroblasts (Allgower, 1956). It
is our view that, at least, a good portion of the granulation tissue is made
up by the proliferation of fibroblasts around the wound, as Grillo (1964)
has demonstrated. We do not exclude the possibility that some of the
cells of the granulation tissue come from cell transformation either from
local cell populations or from distant sources.
III. The Specificity of the Growth-Promoting Effects of Damage
For some time it has been assumed that damage-induced growth is
nonspecific (Cameron, 1955; Washburn, 1960). Recently, evidence has
been presented that suggests that damage-induced growth may be
specific (Bullough and Laurence, 1960a). Therefore it is important for
us to review the evidence for the specificity of growth induced by damage.
Inflammation has been considered a source of growth-promoting substances in wound healing (Menkin, 1941). However, in most experiments
done to show that inflammation contains growth-promoting substances,
the production of inflammation is accompanied by cell death. Therefore
it never is clear whether the accompanying proliferative effects are, in
fact, the result of the inflammatory response or of the release of substances from the damaged or killed cells. To prove that inflammation is
responsible for the growth seen after damage, one must show that
inflammation alone, without any cell necrosis, is capable of stimulating
growth. The evidence we present below strongly suggests that inflammation alone is not capable of stimulating tissue growth.
Bullough and Laurence (1960a) have shown that if one scrapes underneath the center surface of a flap of skin and the flap of skin is sutured
back in place, the epidermis overlying the scraped skin does not undergo
proliferation. Yet, a full inflammatory response occurs in the scraped
area. This is true even if the scraping denudes all the layers of the skin
up to 0.1 mm from the basal layer of the epidermis. We have been able
to show that if one, in a similar way, scrapes the undersurface of a flap
of mouse skin, an inflammatory response occurs underneath the resting
hair follicles, but the hair follicles are not stimulated to grow (Argyris,
1964). The implantation of paraffin beads subcutaneously, under a
portion of skin from which the panniculus carnosus has been previously
13
most experimental animals it is the loose areolar connective tissue in
the subcutis, and beneath the layer of skin muscle, the panniculus
carnosus, that are the primary sources of the granulation tissue (Grillo,
1964; Russell and Billingham, 1962), although it is still possible that some
of the granulation tissue arises from cells that migrate into the wound via
the blood vessels and differentiate into fibroblasts (Allgower, 1956). It
is our view that, at least, a good portion of the granulation tissue is made
up by the proliferation of fibroblasts around the wound, as Grillo (1964)
has demonstrated. We do not exclude the possibility that some of the
cells of the granulation tissue come from cell transformation either from
local cell populations or from distant sources.
III. The Specificity of the Growth-Promoting Effects of Damage
For some time it has been assumed that damage-induced growth is
nonspecific (Cameron, 1955; Washburn, 1960). Recently, evidence has
been presented that suggests that damage-induced growth may be
specific (Bullough and Laurence, 1960a). Therefore it is important for
us to review the evidence for the specificity of growth induced by damage.
Inflammation has been considered a source of growth-promoting substances in wound healing (Menkin, 1941). However, in most experiments
done to show that inflammation contains growth-promoting substances,
the production of inflammation is accompanied by cell death. Therefore
it never is clear whether the accompanying proliferative effects are, in
fact, the result of the inflammatory response or of the release of substances from the damaged or killed cells. To prove that inflammation is
responsible for the growth seen after damage, one must show that
inflammation alone, without any cell necrosis, is capable of stimulating
growth. The evidence we present below strongly suggests that inflammation alone is not capable of stimulating tissue growth.
Bullough and Laurence (1960a) have shown that if one scrapes underneath the center surface of a flap of skin and the flap of skin is sutured
back in place, the epidermis overlying the scraped skin does not undergo
proliferation. Yet, a full inflammatory response occurs in the scraped
area. This is true even if the scraping denudes all the layers of the skin
up to 0.1 mm from the basal layer of the epidermis. We have been able
to show that if one, in a similar way, scrapes the undersurface of a flap
of mouse skin, an inflammatory response occurs underneath the resting
hair follicles, but the hair follicles are not stimulated to grow (Argyris,
1964). The implantation of paraffin beads subcutaneously, under a
portion of skin from which the panniculus carnosus has been previously