Attachment of smooth muscle cells to collagen and their migration toward platelet-derived growth factor.

Abstract

Smooth muscle cells use fibronectin to bind to type I and type Im collagens but bind to type V collagen by a trypsin-resistant intrinsic glycoconjugate. The binding site on type V collagen is located in the aA chain. By using collagen-coated filters in a modified Boyden chamber assay for chemotaxis, it was observed that the platelet-derived growth factor was chemotactic for smooth muscle cells but that several other growth factors were inactive. We suggest that the migration of smooth muscle cells from the media to the intima of a blood vessel, which leads to the formation of an atherosclerotic plaque, may be the result of a chemotactic migration of cells responsive to the platelet-derived growth factor.Smooth muscle cells are connective tissue cells that are present in blood vessels and other pulsatile tissues. These cells synthesize various matrix proteins including proteoglycan (1), elastin (2), and types I, III, and V collagen (3)(4)(5)(6). Because atherosclerotic plaques are composed in large part of smooth muscle cells and the extracellular products they produce (7), there is much interest in factors that regulate the growth and distribution of these cells.Current theories suggest that the formation of the atherosclerotic plaque is initiated at sites where endothelial cells are lost from the basement membrane (for reviews, see refs. 7-9), leading to an accumulation ofplatelets and other blood elements at those sites. Under such conditions, platelets release the platelet-derived growth factor (PDGF), a potent mitogen for smooth muscle but not for endothelial cells (10,11). It is assumed that PDGF causes the proliferation of smooth muscle cells beyond the basement membrane to the inner surface of the blood vessel. Interestingly, Benditt and Benditt (12) found that the cells in many plaques are monoclonal suggesting that a single cell or a single type of cell (13) proliferated to form a plaque.Recently, we and others have studied the attachment and migration of connective tissue cells. Fibroblasts, for example, are attracted to lymphokines (14), macrophage factors (15), activated serum (16), fibronectin (17), the cell binding fragment of fibronectin (18), and collagen fragments (19). Fibroblasts require a substrate of collagen of types I-IV for attachment and migration in the Boyden chamber assays for chemotaxis (14).Here, we confirm earlier work on smooth muscle cells that indicates that smooth muscle cells use fibronectin to attach to types I and III collagens (20). We have extended these studies to show that smooth muscle cells attach preferentially to type V collagen without a requirement for fibronectin. When attached to collagen, the cells migrate toward PDGF in the Boyden chamber assay for chemotaxis. The chemotactic activity of PDGF may be of importance in the early stages of atherosclerosis.MATERIALS AND METHODS Materials. Tissue culture media were purchased from GIBCO. Fetal calf serum and bovine serum albumin were obtained from Reheis Chemical (Kankakee, IL). Trypsin and elastase were fro...

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