Similar involvement of VIP receptor type I and type II in lymphocyte chemotaxis.
Effects of vasoactive intestinal peptide (VIP) on T cell migration are mediated by structurally distinct types I (VIPR1) and II (VIPR2) G protein-associated receptors. The two receptor types were proposed to transduce opposite effects on human T cells, since cytokine-induced chemotaxis of VIPR1-bearing HuT 78 human T cells, in contrast to T cells that express VIPR2, was inhibited by VIP. We studied chemotactic effects of VIP and related agonists with different affinities for VIP- and peptide histidine-isoleucine (PHI)-related receptors. All, VIP, secretin (SEC), a specific ligand for VIPR1, helodermin (HEL), an activator of helodermin-preferring VIPR2, as well as PHI, stimulated chemotaxis into micropore filters of both normal human peripheral blood T and B cells. Involvement of VIPRs was supported by inhibition of VIP-related agonist-induced migration of T and B cells with a VIPR antagonist. Peripheral blood lymphocyte (PBL) chemotaxis to VIP, SEC, HEL and PHI was reduced by inhibition of tyrosine kinase and pertussis or cholera toxin, whereas inhibition of protein kinase C only affected SEC-induced chemotaxis of PBL significantly. VIP-related agonists induced deactivation of migration at high concentrations. Findings in PBL suggest that VIPR1 activation can stimulate normal T and B cell chemotaxis. Different signaling mechanisms may be involved in mediating chemotactic activation of VIPRs and PHIRs, which may allow further exploration of receptor-dependent mechanisms and signaling pathways of VIP as mediator of PBL functions.
Department of Medicine, University of Innsbruck, Austria.
P
P
Schratzberger
A
A
Geiseler
S
S
Dunzendorfer
N
N
Reinisch
C M
CM
Kähler
C J
CJ
Wiedermann
D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D002772:Cholera Toxin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D010770:Phosphotransferases / Q000037:antagonists & inhibitors; D018005:Receptors, Vasoactive Intestinal Peptide / Q000187:drug effects / Q000502:physiology*; D012633:Secretin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D018005:Receptors, Vasoactive Intestinal Peptide; D010566:Virulence Factors, Bordetella; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; C040442:heliodermin; D002772:Cholera Toxin; D010770:Phosphotransferases