Substance P promotes lymphocyte-endothelial cell adhesion preferentially via LFA-1/ICAM-1 interactions.
Substance P (SP), an 11 amino acid peptide, is released by C and A delta sensory nerve fibers during tissue insult and inflammation. We investigated the effect of SP on the expression and avidity of adhesion molecules, on lymphocytes and endothelial cells, which are central to the inflammatory cascade. Using in vitro adhesion assays we found that pretreatment of murine endothelial cells with SP enhanced their adhesiveness to splenocytes, the murine T cell hybridoma EL4 and nylon-enriched primary murine T cells in a dose and time dependent manner, the optimum dose being 10(-10) M and the optimum time 6 h. SP at 10(-10) M was also able to stimulate the splenocytes, EL4 T cells and primary T cells to enhance their adhesiveness for endothelial cells. The increased adhesiveness was associated with enhanced expression of ICAM-1 on endothelial cells and increased avidity of LFA-1 on lymphocytes. Further SP was chemotactic for T cells. These data suggest that SP modulates lymphocyte-endothelial cell interactions by preferentially upregulating LFA-1 and ICAM-1 interactions.
Vishwanath
R
R
Microbiology Division, National Institute of Immunology, New Delhi, India.
Mukherjee
R
R
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology*; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D008214:Lymphocytes / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D013373:Substance P