Human T lymphocyte chemotaxis and adhesion induced by vasoactive intestinal peptide.
Vasoactive intestinal peptide (VIP), a 28-amino acid peptide of the glucagon-secretin family, has been reported to have significant immunoregulatory properties. In the present study, we demonstrate that VIP has potent chemotactic effects on T lymphocytes. At concentrations of between 10(-8) and 10(-9) M, VIP stimulated significant in vitro chemotaxis of T lymphocytes from both CD4+ and CD8+ subsets. VIP produced more potent chemotactic effects on unstimulated T cells than on anti-CD3-activated cells. Following anti-CD3 activation, binding of 125I-labeled VIP to T cells was reduced and this correlated with a reduction in receptor number without any change in affinity. Preincubation of unstimulated T cells with VIP produced increases in adhesion to ICAM and VCAM integrins. In addition, VIP pretreatment significantly increased unstimulated T cell adhesion to the extracellular matrix protein fibronectin. However, VIP induced less binding of activated T cells to fibronectin. Taken together these results suggest that VIP is a potent chemoattractant and stimulant of adhesion for T lymphocytes. In contrast to chemokines that are more active on stimulated T cells, such as RANTES, this neuropeptide preferentially targets unactivated T cells, suggesting that it may play a greater role in homing and distribution of lymphocytes.
Johnston
J A
JA
Laboratory of Molecular Immunoregulation, Program Resources, Inc./Dyncorp, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702.
Taub
D D
DD
Lloyd
A R
AR
Conlon
K
K
Oppenheim
J J
JJ
Kevlin
D J
DJ
D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects; D018946:Chemokine CCL5; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000494:pharmacology; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D018946:Chemokine CCL5; D008222:Lymphokines; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide