Interaction of human neutrophils and HL-60 cells with the extracellular matrix.

The accumulation of polymorphonuclear leukocytes (PMNs) at sites of inflammation or injury is generally attributed to the presence of chemoattractants and agents that increase PMN adherence. Extracellular matrix (ECM) proteins released at these sites may promote or modulate PMN adhesion, motility, oxidant generation, degranulation, and phagocytosis, but their role in these processes is not well defined. Of particular interest are thrombospondin (TSP), a 450 kD ECM protein released by activated platelets, and vitronectin (VN), a major constituent of plasma. Low concentrations of soluble TSP prime for both N-formyl-methionyl-leucyl-phenylalanine (FMLP)-mediated O2- generation and chemotaxis, whereas VN suppresses FMLP-mediated O2- generation but primes for FMLP-mediated chemotaxis. TSP alone, at high concentrations, stimulates chemotaxis of PMNs, whereas VN, at the same concentrations, fails to stimulate chemotaxis. In contrast to soluble ECM proteins, substrate bound TSP, laminin, and VN promote PMN adhesion and random migration. As functional studies suggest, unactivated PMNs express receptors for both TSP and VN, and both TSP and VN receptor expression increases substantially following PMN activation. PMN-like HL-60 cells interact similarly with ECM proteins, and thus provide an important model for studying the expression of ECM receptors and the acquisition of ECM-mediated functional responses during blood cell differentiation. The ability of PMNs to interact with ECM proteins and modulate ECM protein receptors suggests that these proteins, alone or in synergy with chemotactic peptides, play an important role in regulating PMN diapedesis.