EFFECTS OF EXTRACELLULAR-MATRIX PROTEINS ON MACROPHAGE DIFFERENTIATION, GROWTH, AND FUNCTION - COMPARISON OF LIQUID AND AGAR CULTURE SYSTEMS

Both spaceflight and skeletal unloading suppress the haematopoietic di fferentiation of macrophages (Sonnenfeld et al., Aviat. Space Environ. Med., 61:648-653, 1990; Armstrong et al., J. Appl. Physiol., 75:2734- 2739, 1993). The mechanism behind this reduction in haematopoiesis has yet to be elucidated. However, changes in bone marrow extracellular m atrix (ECM) may be involved. To further understand the role of ECM pro ducts in macrophage differentiation, we have performed experiments eva luating the effects of fibronectin, laminin, collagen type I, and coll agen type TV on macrophage development and function. Bone marrow-deriv ed macrophages cultured on four different ECM substrates in liquid cul ture medium showed less growth than those cultured on plastic. Signifi cant morphological differences were seen on each of the substrates use d. Phenotypically and functionally, as measured by class If major hist ocompatibility molecule (MHCII) expression, MAC-2 expression, and the secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF -alpha), these macrophages were similar. In contrast, bone marrow-deri ved macrophages cultured in suspension, using agar, showed no differen ce in growth when exposed to ECM proteins. However, IL-6 and TNF-alpha secretion was affected by fibronectin, laminin, collagen type I, and collagen type TV in a concentration-dependent manner. We conclude that the ECM products fibronectin, laminin, collagen type I, and collagen type TV have profound effects on macrophage development and function. Additionally, we suggest that an ECM-supplemented agar culture system provides an environment more analogous to in vivo bone marrow than doe s a traditional liquid culture system. (C) 1994 Wiley-Liss, Inc.