Differential inside-out activation of beta2-integrins by leukotriene B4 and fMLP in human neutrophils.
We have investigated how LTB4, an endogenous chemoattractant encountered early in the inflammatory process, and fMLP, a bacteria-derived chemotactic peptide emanating from the site of infection, mediate inside-out regulation of the beta2-integrin. The role of the two chemoattractants on beta2-integrin avidity was investigated by measuring their effect on beta2-integrin clustering and surface mobility, whereas their effect on beta2-integrin affinity was measured by the expression of a high affinity epitope, a ligand-binding domain on beta2-integrins, and by integrin binding to s-ICAM. We find that the two chemoattractants modulate the beta2-integrin differently. LTB4 induces an increase in integrin clustering and surface mobility, but only a modest increase in integrin affinity. fMLP evokes a large increase in beta2-integrin affinity as well as in clustering and mobility. Lipoxin, which acts as a stop signal for the functions mediated by pro-inflammatory agents, was used as a tool for further examining the inside-out mechanisms. While LTB4-induced integrin clustering and mobility were inhibited by lipoxin, only a minor inhibition of fMLP-induced beta2-integrin avidity and no inhibition of integrin affinity were detected. The different modes of the inside-out regulation of beta2-integrins suggest that distinct mechanisms are involved in the beta2-integrin modulation induced by various chemoattractants.
Division of Cell Biology/IBK, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
Veronika
V
Patcha
Jane
J
Wigren
Martin E
ME
Winberg
Birgitta
B
Rasmusson
Jianxun
J
Li
Eva
E
Särndahl
D018821:CD18 Antigens / Q000378:metabolism*; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism*; D008024:Ligands; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D018821:CD18 Antigens; D008024:Ligands; D007975:Leukotriene B4