VI SOURCE OF GRANULATION TISSUE 69 1 



by time lapse cinephotography of fibroblast cultures; or in fixed histological 

 sections of wounds. Some investigators (Ebert et al., 1939) believe that the mono- 

 cytes are capable of transformation to macrophages and ultimately into fixed 

 tissue histiocytes. The function of macrophage cells appears to be ingestion of 

 erythrocytes and other clot elements. Certain cells of the reticulo-endothelial 

 system remain undetected unless specifically stained by means of their cytoplasmic 

 affinity for metallic salts (Marshall, 1946, 1948). These can be classified into two 

 types. One consists of mononuclear cells which occur in increasing numbers 

 during the period when leukocytes are degenerating. They enlarge and develop 

 into ameboid macrophages, whose function is phagocytosis. The second type of 

 metalophillic cell is elongated, either rod-shaped or with a slightly branching 

 cytoplasm and can be found in decreasing numbers in the adjacent normal 

 tissue. The close association with fibroblasts and presence in areas where reticulin 

 and collagen are being formed has suggested that these cells become transformed 

 into fibroblasts (Marshall, 1953). 



Fibroblast migration into the wound area occurs relatively early and has l^een 

 studied extensively by Stearns (1939, 1940a, h). Initially the cells are stellate in 

 shape and irregularly oriented, but eventually they realign parallel to the new- 

 vessels (Howes, 1957). The tension forces which guide their shape and alignment 

 as well as theories concerning their source have been discussed in other parts of 

 this chapter. 



(c) Most probably both local and distant cells play an active role in wound 

 healing. The initial response and subsequent phagocytic activity are undoubtedly 

 brought about by cells of the vascular system, following which, adjacent fibroblasts 

 and scattered fixed cells of the reticulo-endothelial system assume the role of 

 forming granulation tissue. However, there is much about this latter process 

 which remains obscure. 



VII. FIBROBLASTIC PROLIFERATION 



The immediate expansion and ultimate contraction of a wound (Billingham and 

 Russell, 1956; Abercrombie and James, 1957) exerts a profound influence upon 

 stress patterns both within and without the defect. Fibroblastic proliferation as 

 well as orientation of cells in adjacent normal skin are governed by these varying 

 stress patterns. Initially the tensile forces are produced from without the wound. 

 This phase persists for only 1-2 days, hence its eflfects upon cell orientation are 

 limited. The natural elasticity of skin causes a separation of the cut edges which 

 in turn evokes forces within the clot, directed perpendicular to the margins. There 

 is considerable evidence to indicate that tension within a clot can directly influence 

 orientation of its contained cells. 



The production of a wound produces a leakage of blood from the damaged 

 vessels. The subsequent clotting of this blood leaves the defect filled with a matrix 

 bound together by a dense meshwork of fibrin stands (Hudack and Blunt, 1950). 

 In clots formed by bovine fibrinogen and thrombin, the fibrinogen molecules are 

 polymerized by the action of thrombin to form needle-shaped protofibrils; these 



Literature p. 703 



