ACTIVATION OF HUMAN LYMPHOMONONUCLEAR CELLS BY PEPTIDES DERIVED FROM EXTRACELLULAR-MATRIX PROTEINS

A series of peptides of 15 amino acids with sequences contained in hum an extracellular matrix (ECM) proteins (fibronectin, laminin A, lamini n B1, tenascin, undulin, alpha(1)-chain of type IV and VIII collagen a nd alpha(2)-chain of type VIII collagen) have been synthesized. The se lected structures conformed to the following pattern: (i) Pro at posit ion 6, (ii) Leu, Lys, lie, Val, Ala or Gly at position 2, (iii) Glu or Asp at position 11. Fibronectin and the indicated peptides, when pres ent in cultures of lymphomononuclear cells from healthy donors, promot ed stimulation of monocytes manifested by a release of IL-1 alpha IL-1 beta, IL-6 and TNF alpha; an increase in the percentage of cells expr essing CD14, CD16, CD11b and CD14/CD16; an increase in cytotoxicity ag ainst HT-29. Cytotoxicity against K562 and Daudi cells (targets of NI( and Wt cells) was also observed together with an increase in the perc entage of cells expressing CD56, CD56/CD16 (corresponding to NK cells) , and CD56/CD8 (corresponding to NK-like lymphocytes), indicating a st imulation of lymphocytes. Activated monocytes and lymphocytes containe d a large number of granules with DNAse activity. These results sugges t that at least some of the immunological properties of ECM proteins c ould be accounted for by motifs fulfilling a characteristic sequence p attern shared by all of them.