Differential inside-out activation of β2 integrins by leukotriene B4 and fMLP in human neutrophils

Patcha Brodin, VeronikaLinköpings universitet,Medicinsk mikrobiologi,Hälsouniversitetet (författare)

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 β2-integrin. The role of the two chemoattractants on β2-integrin avidity was investigated by measuring their effect on β2-integrin clustering and surface mobility, whereas their effect on β2-integrin affinity was measured by the expression of a high affinity epitope, a ligand-binding domain on β2-integrins, and by integrin binding to s-ICAM. We find that the two chemoattractants modulate the β2-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 β2-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 β2-integrin avidity and no inhibition of integrin affinity were detected. The different modes of the inside-out regulation of β2-integrins suggest that distinct mechanisms are involved in the β2-integrin modulation induced by various chemoattractants.

Wigren, JaneLinköpings universitet,Medicinsk mikrobiologi,Hälsouniversitetet(Swepub:liu)janwi24 (författare)
Winberg, Martin E. (författare)
Rasmusson, BirgittaLinköpings universitet,Medicinsk mikrobiologi,Hälsouniversitetet(Swepub:liu)birra51 (författare)
Li, JianxunDepartment of Oral Biology, College of Dentistry, University of Illinois, Chicago, USA (författare)
Särndahl, EvaLinköpings universitet,Cellbiologi,Hälsouniversitetet(Swepub:liu)evasa98 (författare)
Linköpings universitetMedicinsk mikrobiologi (creator_code:org_t)

Ingår i:Experimental Cell Research: Elsevier BV300:2, s. 308-3190014-48271090-2422

Av författaren/redakt...: Patcha Brodin, V ...; Wigren, Jane; Winberg, Martin ...; Rasmusson, Birgi ...; Li, Jianxun; Särndahl, Eva

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