title: Activation of the beta2 integrin Mac-1 (CD11b/CD18) by an endogenous lipid mediator of human neutrophils and HL-60 cells.
abstract: beta2 integrins (CD11/CD18) play a key role in the adhesion, activation, migration and phagocytosis of human neutrophils. In order to exert their functions, beta2 integrins require activation, which results in an enhancement of ligand affinity. This functional up-regulation is probably due to a conformational change of the beta2 integrins, but the mechanisms of inside-out signaling that trigger this activation are still under investigation. In the present study, the effect of cellular lipids on the affinity state of beta2 integrins was investigated. Lipids were extracted from human neutrophils and HL-60 cells after stimulation with IL-8 or phorbol ester, respectively. The extracts were purified by anion exchange chromatography and/or HPLC fractionation. The lipid extracts induced the adhesion of neutrophils to fibrinogen and, in a cell-free assay system, the binding of C3bi-coated zymosan-particles by purified beta2 integrin Mac-1 (CD11b/CD18). The integrin up-regulating activity was resistant to ester hydrolysis, eluted as one particular HPLC-fraction, and showed an absorption maximum at 194+/-2 nm. Taken together, these data support the concept that activated neutrophils and HL-60 cells can generate an endogenous lipid mediator, which up-regulates ligand binding activity of beta2 integrins.
authors.affiliation: Department of Physiology, Freie Universität Berlin, Berlin-Dahlem, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Klugewitz
authors.forename: K
authors.initials: K
authors.lastname: Ley
authors.forename: D
authors.initials: D
authors.lastname: Schuppan
authors.forename: R
authors.initials: R
authors.lastname: Nuck
authors.forename: P
authors.initials: P
authors.lastname: Gaehtgens
authors.forename: B
authors.initials: B
authors.lastname: Walzog
mesh_terms: D018821:CD18 Antigens / Q000378:metabolism*; D018922:HL-60 Cells / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018821:CD18 Antigens