INHIBITION OF T-CELL ADHESION TO EXTRACELLULAR-MATRIX GLYCOPROTEINS BY HISTAMINE - A ROLE FOR MAST-CELL DEGRANULATION PRODUCTS

Mast cells, which are capable of releasing a multitude of preformed an d newly generated biological mediators and cytokines, are involved in various inflammatory processes. We studied whether histamine, a mast c ell degranulation product, influences the adhesive interactions of T c ells with extracellular matrix (ECM) glycoproteins, an event that occu rs at sites of inflammation and is mediated primarily by virtue of cel l-surface receptors of the beta 1-integrin subfamily. A prerequisite o f lymphocyte-ECM interactions is activation of the cells, which modula tes the affinity of the otherwise inactive integrins. Isolated rat CD4 (+) T cells were preincubated with histamine and activated with phorbo l myristate acetate (PMA), and their ability to adhere to immobilized ECM components (fibronectin and laminin) was determined. Preincubation with histamine resulted in a 40-50% decrease in the adhesion of the C D4(+) cells to both fibronectin or laminin. The notion that inhibition of T cell adhesion to ECM proteins by histamine-induced increase of t he cells' intracellular levels of cAMP, thus interfering with calcium influx-associated events that occur during T cell. activation, is supp orted by the finding that T cell adhesion was also abrogated by pharma cological inducers of cAMP. When the T cells were preincubated with su pernatants of immunologically activated mast cells and then activated with PMA, a 40-50% inhibition of their adhesion to fibronectin or lami nin was also observed. The inhibitory moiety present in the mast cell degranulation supernatants was resistant to heat (80 degrees C). Hista mine exerted its suppressive effect on adhesion of T cells via their H p receptors, as pretreatment with Hp antagonists abrogated the inhibit ory effect. Thus, both purified histamine and mast cell-secreted hista mine appear to be capable of affecting T cell interactions with ECM.