Lysophospholipids control integrin-dependent adhesion in splenic B cells through G(i) and G(12)/G(13) family G-proteins but not through G(q)/G(11).
Integrin-mediated adhesion is a crucial step in lymphocyte extravasation and homing. We show here that not only the chemokines CXCL12 and CXCL13 but also the lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) enhance adhesion of murine follicular and marginal zone B cells to ICAM-1 in vitro. This process involves clustering of integrin LFA-1 and is blocked by pertussis toxin, suggesting that G(i) family G-proteins are involved. In addition, lysophospholipid-induced adhesion on ICAM-1 depends on Rho and Rhokinase, indicative of an involvement of G(12)/G(13), possibly also G(q)/G(11) family G-proteins. We used G(12)/G(13)- or G(q)/G(11)-deficient B cells to study the role of these G-protein families in lysophospholipid-induced adhesion and found that the pro-adhesive effects of LPA and S1P are completely abrogated in G(12)/G(13)-deficient marginal zone B cells, reduced in G(12)/G(13)-deficient follicular B cells, and normal in G(q)/G(11)-deficient B cells. We also show that loss of lysophospholipid-induced adhesion results in disinhibition of migration in response to the follicular chemokine CXCL13, which might contribute to the abnormal localization of splenic B cell populations observed in B cell-specific G(12)/G(13)-deficient mice in vivo. Taken together, this study shows that lysophospholipids regulate integrin-mediated adhesion of splenic B cells to ICAM-1 through G(i) and G(12)/G(13) family G-proteins but not through G(q)/G(11).
Rieken
Stefan
S
Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg, Germany.
Herroeder
Susanne
S
Sassmann
Antonia
A
Wallenwein
Barbara
B
Moers
Alexandra
A
Offermanns
Stefan
S
Wettschureck
Nina
N
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002448:Cell Adhesion; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000737:chemistry / Q000502:physiology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000737:chemistry / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D013154:Spleen / Q000166:cytology* / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases
D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D018799:Intercellular Adhesion Molecule-1; C060506:sphingosine 1-phosphate; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D019204:GTP-Binding Proteins; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020741:rho GTP-Binding Proteins; D013110:Sphingosine; C032881:lysophosphatidic acid