Inhibition of T cell adhesion to extracellular matrix glycoproteins by histamine: a role for mast cell degranulation products

• Published in: Journal of leukocyte biology 1994-10, Vol.56 (4), p.495-501
• Main Authors: Hershkoviz, Rami, Lider, Ofer, Baram, Dana, Reshef, Tamar, Miron, Shmuel, Mekori, Yoseph A.
• Format: Article
• Language: English
• Subjects: adhesion; Animals; Bucladesine - pharmacology; Calcium - metabolism; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - metabolism; Cell Adhesion - drug effects; Cell Adhesion Molecules - metabolism; Cell Degranulation; Colforsin - pharmacology; Down-Regulation; extracellular; Extracellular Matrix Proteins - metabolism; Fibronectins - metabolism; histamine; Histamine - pharmacology; Humans; Integrins - metabolism; Laminin - metabolism; mast cell; Mast Cells - physiology; matrix; Rats; Rats, Inbred Lew; Receptors, Histamine H2 - physiology; Second Messenger Systems; T cell
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.56.4.495

Mast cells, which are capable of releasing a multitude of preformed and newly generated biological mediators and cytokines, are involved in various inflammatory processes. We studied whether histamine, a mast cell degranulation product, influences the adhesive interactions of T cells with extracellular matrix (ECM) glycoproteins, an event that occurs at sites of inflammation and is mediated primarily by virtue of cell‐surface receptors of the β1‐integrin subfamily. A prerequisite of lymphocyte‐ECM interactions is activation of the cells, which modulates the affinity of the otherwise inactive integrins. Isolated rat CD4+ T cells were preincubated with histamine and activated with phorbol 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 CD4+ cells to both fibronectin or laminin. The notion that inhibition of T cell adhesion to ECM proteins by histamine‐induced increase of the cells' intracellular levels of cAMP, thus interfering with calcium influx‐associated events that occur during T cell activation, is supported by the finding that T cell adhesion was also abrogated by pharmacological inducers of cAMP. When the T cells were preincubated with supernatants of immunologically activated mast cells and then activated with PMA, a 40–50% inhibition of their adhesion to fibronectin or laminin was also observed. The inhibitory moiety present in the mast cell degranulation supernatants was resistant to heat (80°). Histamine exerted its suppressive effect on adhesion of T cells via their H2 receptors, as pretreatment with H2 antagonists abrogated the inhibitory effect. Thus, both purified histamine and mast cell‐secreted histamine appear to be capable of affecting T cell interactions with ECM. J. Leukoc. Biol. 56: 495–501; 1994.