Studies on inflammation and wound healing: angiogenesis and collagen synthesis stimulated in vivo by resident and activated wound macrophages.

Wound inflammatory cells were harvested by aspiration of fluid from the "dead space" of subcutaneous rabbit wounds and transplanted into the cornea where, compared with suitable controls, they stimulated healing (i.e., angiogenesis, fibroplasia, and new collagen synthesis, which led to formation of visible, vascularized scar tissue). Analysis of the data and the literature supports the conclusions that: (1) inflammatory cells control the continuation of the repair process after the immediate effects of injury subside; (2) macrophages, as opposed to granulocytes, appear to be the major contributors; (3) activated by their presence in the wound, macrophages release substances that stimulate fibroplasia, collagen synthesis, and angiogenesis in vivo; and (4) tissue injury is not a maximum stimulus to repair, since endotoxin-treated macrophages have increased capacity to stimulate collagen synthesis and angiogenesis. A hypothesis is offered to explain the notorious clinical discrepancy between the extent of injury and the extent of repair.

Role of platelets and fibrin in the healing sequence: an in vivo study of angiogenesis and collagen synthesis.

UNLABELLED: The signals that initiate repair are poorly characterized. These studies investigate the capacity of platelets and fibrin to initiate angiogenesis, fibroplasia, collagen synthesis and monocyte migration in the rabbit cornea assay. METHODS: Autologous platelets and platelet-free fibrin were isolated from rabbit blood. Released and control platelet preparations and autologous and commercial fibrin were implanted in rabbit corneas. RESULTS: Thrombin-released platelets produced angiogenesis and opacification. Histology showed fibroplasia, corneal thickening, and neovascularization. Collagen synthesis was elevated to twice control levels in thrombin-activated platelet preparations. Various control platelet preparations produced no angiogenesis, no opacification, and no histologic change. All fibrin injections elicited a cellular exudate from the limbal vessels, followed by angiogenesis and corneal opacification. Histology showed a mononuclear infiltrate with neovascularization and fibroplasia. Control injections of rabbit skin collagen and fibroblasts produced no response.

Production a corpus luteum angiogenic factor responsible for proliferation of capillaries and neovascularization of the corpus luteum.

Factors controlling the changes in the vascular pattern of the ovary that occur during the reproductive cycle have been investigated. By using the rabbit cornea, the abilities of ovarian corpus luteum and of follicles to induce neovascularization have been compared. While the corpus luteum is capable of inducing neovascularization, the follicles do not have this ability. It is therefore likely that the corpus luteum actively participates in its own neovascularization by secreting a factor that we have called "corpus leutem angiogenic factor" (CLAF).